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1-1-2012

Organization of nuclei

George Paxinos University Of New South Wales, Research Australia

Xu-Feng Huang University of Wollongong, [email protected]

Gulgun Sengul Ege University

Charles Watson Curtin University,Neuroscience Research Australia

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Recommended Citation Paxinos, George; Huang, Xu-Feng; Sengul, Gulgun; and Watson, Charles: Organization of brainstem nuclei 2012, 260-327. https://ro.uow.edu.au/hbspapers/3056

Research Online is the open access institutional repository for the University of Wollongong. For further information contact the UOW Library: [email protected] Organization of brainstem nuclei

Abstract This chapter describes homologs of nuclei identified in the brainstem of other and attempts to extend to the human the overall organizational schemata that have been proposed for the brainstem of other mammalian species. We present herein updated diagrams of the Atlas of the Human Brainstem (Paxinos and Huang, 1995). The diagrams have been thoroughly revised in light of our recent work on the rat (Paxinos and Watson, 2007) and rhesus monkey (Paxinos et al., 3rd ed, in BrainNavigator, , 2010) as well as our work on the marmoset (Atlas of the Marmoset in Stereotaxic Coordinates, Paxinos et al., (2012)).

Keywords organization, nuclei, brainstem

Disciplines Arts and Humanities | Life Sciences | Medicine and Health Sciences | Social and Behavioral Sciences

Publication Details Paxinos, G., Huang, X., Sengul, G. & Watson, C. (2012). Organization of brainstem nuclei. The Human (pp. 260-327). Amsterdam: Elsevier Academic Press.

This book chapter is available at Research Online: https://ro.uow.edu.au/hbspapers/3056 CHAPTER 8

Organization of Brainstem Nuclei George Paxinos 1, 2, Huang Xu-Feng 3, Gulgun Sengul 4, Charles Watson 1, 5 1 Neuroscience Research Australia, Sydney, Australia, 2 The University of New South Wales, Sydney, Australia, 3 University of Wollongong, Wollongong, Australia, 4 Ege University, School of Medicine, Department of , Bornova, Izmir, Turkey, 5 Faculty of Health Sciences, Curtin University, Perth, Australia

OUTLINE

Abbreviations Used in the Figures 262 309 Epicoeruleus 310 Autonomic Regulatory Centers 300 Dorsal Motor Nucleus of Vagus 300 310 300 Raphe Obscurus and Magnus Nuclei 310 302 Median and Paramedian Raphe Nuclei 311 303 Raphe Pontis Nucleus 311 311 304 Intermediate Reticular Zone 304 Ventral Mesencephalic and Substantia Historical Considerations 304 Nigra 312 Position 304 Caudal Linear Nucleus 312 Cells 304 Interfascicular Nucleus 312 Y 305 Rostral Linear Nucleus 312 305 Retrorubral Fields 312 305 Paranigral Nucleus 312 Salmon -Binding Sites 305 Parabrachial Pigmented Nucleus 312 Connections 305 312 Retroambiguus and Ambiguus Nuclei 306 313 Ventral, Medial, and Dorsal Reticular Nuclei 306 Cranial Motor Nuclei 313 Mesencephalic Reticular Formation 306 313 Lateral Reticular Nucleus 307 Facial Nucleus 313 Gigantocellular, Lateral Paragigantocellular, Motor Trigeminal Nucleus 313 Gigantocellular Ventral Part, Gigantocellular 313 Alpha Part, and Dorsal Paragigantocellular, 313 and Parvicellular Reticular Nuclei 307 313 Tegmental Nuclei 308 314 Ventral Tegmental Nucleus 308 Gracile Nucleus 314 Dorsal Tegmental Nucleus 308 Cuneate Nucleus 314 Posterodorsal Tegmental Nucleus 309 External Cuneate Nucleus 314 Laterodorsal Tegmental Nucleus 309 Pericuneate, Peritrigeminal, X, and Paratrigeminal Pedunculotegmental Nucleus 309 Nuclei 314 Microcellular Tegmental Nucleus 309 Medial Pericuneate Nucleus 314

The Human Nervous System, Third Edition DOI: 10.1016/B978-0-12-374236-0.10008-2 260 Copyright Ó 2012 Elsevier Inc. All rights reserved. ORGANIZATION OF BRAINSTEM NUCLEI 261

Lateral Pericuneate Nucleus 314 318 Peritrigeminal Nucleus 314 Parabigeminal Nucleus 318 Afferent Connections of the Pericuneate Medial Terminal Nucleus of the Accessory Optic and Peritrigeminal Nuclei 315 Tract 318 Nucleus X 315 Precerebellar Nuclei and 318 Paratrigeminal Nucleus 315 Spinal Trigeminal Nucleus 316 Inferior Olive 319 Medial Accessory Olive 319 Mesencephalic Trigeminal Nucleus 316 Beta Nucleus 319 Endolemniscal Nucleus 316 Dorsomedial Column 319 B9 and Supralemniscal Nucleus 316 Ventrolateral Outgrowth 319 316 Cap of Kooy 319 Medial Vestibular Nucleus 316 Dorsal Accessory Olive 319 Spinal Vestibular Nucleus 316 Principal Inferior Olive 319 Lateral Vestibular Nucleus 317 Conterminal Nucleus 319 Interstitial Nucleus of the Eighth 317 319 Nucleus of Origin of Vestibular Efferents 317 Paramedian and Dorsal Paramedian Nuclei 320 Intercalated Nucleus 320 Auditory System 317 Prepositus and Interpositus Nuclei 320 Ventral and Dorsal Cochlear Nuclei 317 Cribriform Nucleus 320 Superior Olive 317 Trapezoid Nucleus 317 320 Red Nucleus 321 Nuclei of the Lateral 318 321 318 Nucleus of the Brachium of the Inferior Colliculus 318 Conclusion 321 Medial Geniculate 318 Acknowledgment 321 318

This chapter describes human homologs of nuclei nuclei and areas with discrete emphasis on the struc- identified in the brainstem of other mammals and tural organization of the region, rather than functional, attempts to extend to the human the overall organiza- chemical, or pathological characteristics. It would have tional schemata that have been proposed for the brain- been inappropriate, however, to discount apparent func- stem of other mammalian species. We present herein tional characteristics of some brainstem structures, updated diagrams of the Atlas of the Human Brainstem particularly when such characteristics can be used to (Paxinos and Huang, 1995). The diagrams have been systematize the diversity of brainstem neuronal groups. thoroughly revised in light of our recent work on the This chapter discusses a number of human brainstem rat (Paxinos and Watson, 2007) and rhesus monkey structures in relation to autonomic function, vestibular (Paxinos et al., 3rd ed, in BrainNavigator, Elsevier, system, visual system, auditory system, motor cranial 2010) as well as our work on the marmoset (Atlas of , or somatosensory system. However, many the Marmoset Brain in Stereotaxic Coordinates, Paxinos brainstem structures are not obviously related to et al., (2012)). a particular function, or are related to a number of func- Structures of the brainstem are very diverse with tions or better known for their structural characteristics. respect to functions they participate in, neuroactive Thus, the reticular formation, precerebellar nuclei, red elements they contain, and neural pathways they nucleus, locus coeruleus, and raphe nuclei are distin- accommodate. As a reflection, the anatomical organiza- guished as complex structural entities and discussed tion of the human brainstem is a complex amalgam of in approximate rostrocaudal order. This chapter also compact neuronal groups and dispersed cell areas describes the distribution of some neuroactive chemicals with varying cytoarchitecture. Many of these , to rationalize the details of structural delineations. There nuclei, and areas are given elaborate descriptions in has been considerable on the chemoarchitec- separate chapters of this book that deal with associated ture of the brainstem in other species, most commonly functional networks, whereas the purpose of this in rodents. This chapter, however, focuses on examina- chapter is to present an account of human brainstem tion of human brainstem chemoarchitecture.

III. BRAINSTEM AND 262 8. ORGANIZATION OF BRAINSTEM NUCLEI

Following the original suggestion of Paxinos and stable across mammalian species, this chapter relies Huang (1995), we also acknowledge that the radial mainly on AChE distribution to illustrate brainstem arrangement of the human caudal with refer- homologies. We have also considered cell morphology ence to the (as King, 1980, proposed for and the distribution of hydroxylase (Chapter 13), the cat) is more tenable than the “quilt” pattern hydroxylase (Chapter 11), substance P proposed by Olszewski and Baxter (1954). Thus, it (Halliday et al., 1988a), and (Halliday appears that the human caudal hindbrain is organized et al., 1988c). Some connectivity data were available to roughly in columns, commencing with a special afferent us from therapeutic (Mehler, 1974a). All zone (vestibular nuclei) dorsolaterally and terminating findings reported here concern the human unless other- in a general motor efferent zone ventromedially (hypo- wise stated. glossal). Intervening in a dorsal-to-ventral sequence Figures 8.1–8.64 are updates of the diagrams found in are the somatic afferent column (spinal nucleus of the Atlas of the Human Brainstem (Paxinos, G., and Huang, trigeminal), the visceral afferent column (solitary X.F., 1995, Academic Press, San Diego). The reader can nucleus and the dorsolateral slab of the intermediate find the photographic plates on which the current reticular zone), and the visceral or branchial efferent diagrams are based in the Paxinos and Huang (1995) column (dorsal motor nucleus of vagus, ambiguus, atlas. and the ventromedial part of IRt). A scheme of organiza- The coronal maps of the human brainstem are pre- tion along these lines was suggested by Herrick (1922) sented in sections at 2-mm intervals. The medullary for the cranial nerve nuclei and is now popularly used tissue depicted in Figures 8.1–8.64 was obtained by in many textbooks. Paxinos and Huang (1995) 4 h post mortem from a 59- Traditionally, nuclei have been identified using year-old white male who died suddenly from a cytoarchitecture, myeloarchitecture, and connectivity. attack. The donor had no of any neuro- In the last 20 years, researchers have used develop- logical or psychiatric disease. mental, functional, and, increasingly, chemoarchitec- Naked Arabic numerals have been used to denote tonic criteria to complement these traditional methods cortical areas, cortical layers, cranial nerve nuclei and (Heimer and Wilson, 1975; Krettek and Price, 1978; layers. Having to contend with the cortical Paxinos and Watson, 1998; Koutcherov et al., 2000). areas in , we decided to use A before the We are of the view that for the establishment of homol- Arabic numerals denoting cortical areas. This meant ogies it is necessary that the human and rat brainstem that we could no longer use A1, A8, A11, A13, or A14 be studied in parallel using the same criteria. The for the catecholamine cell groups. The Swedes did not criteria used for establishing homologies in the present know what was noradrenaline (), what study are morphological and include cytoarchitecture, (epinephrine) and what when chemoarchitecture, topography, and subnuclear they discovered these cell groups. Now, however, we organization. know and we have specified them by changing to A1 Work based on chemoarchitectonic analysis began to NA1, C1 to Ad1, A5 to NA5, A7 to NA7, A8 to after Koelle and Friedenwald (1949) developed a simple DA8, etc. histochemical method for revealing acetylcholinesterase (AChE), the degradative enzyme for . The application of AChE staining has subsequently been ABBREVIATIONS USED IN THE FIGURES proven very useful in distinguishing brain areas. A comprehensive delineation of the rat brain by Paxinos and Watson (1982) was done largely on the basis of 3N oculomotor nucleus AChE reactivity with Nissl staining used as a secondary criterion. In the last 30 years, AChE histochemistry has 3n been successfully used for delineation of the brain in 4N trochlear nucleus many mammalian species. Most importantly, AChE 4n histochemistry works well on the fresh (unfixed) post- 4V 4th ventricle mortem , which allows this method to be successfully applied to the neuroanatomical delineation 5ADi motor trigeminal nucleus, anterior digastric part of the human brain. For example, AChE staining was 5Ma motor trigeminal nucleus, masseter part used in pathological studies of the of patients 5MHy mylohyoid subnucleus of the motor trigeminal nucleus with Alzheimer’s disease (Saper and German, 1987) 5N motor trigeminal nucleus and was employed to reveal the organization of the human (Koutcherov et al., 2000). Because 5PC motor trigeminal nucleus, parvicellular part the AChE content of homologous nuclei is reasonably 5Sol trigeminal-solitary transition zone

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 263

5Sp lamina 5 of the spinal gray Ad1 C1 adrenaline cells 5Pt motor trigeminal nucleus, pterygoid part Ad2 C2 adrenaline cells 5Te motor trigeminal nucleus, temporalis part AHi, amygdalohippocampal area 5Tr trigeminal transition zone AmbC ambiguus nucleus, compact part 6N abducens nucleus AmbL ambiguus nucleus, loose part 6n AmbSC ambiguus nucleus, semicompact part 7DI facial nucleus, dorsal intermediate subnucleus Amg amygdaloid nucleus 7DM facial nucleus, dorsomedial subnucleus ami amiculum of the olive 7I facial nucleus, intermediate part AP 7L facial nucleus, lateral subnucleus APT anterior pretectal nucleus 7N facial nucleus Aq aqueduct 7n Ar arcuate nucleus of the caudal hindbrain 7SH , stylohyoid part asc7 ascending fibers of the facial nerve 7Sp lamina 7 of the spinal gray asp anterior spinal 7VI facial nucleus, ventral intermediate subnucleus Au austral nucleus 7VL facial nucleus, ventrolateral subnucleus AVC anteroventral 7VM facial nucleus, ventromedial subnucleus Bar Barrington’s nucleus 8Sp lamina 8 of the spinal gray B9 B9 serotonin cells 8n BL basolateral amygdaloid nucleus 8vn, vestibular root of the vestibulocochlear nerve basv basal (drains into ) 9n glossopharyngeal nerve bic brachium of the inferior colliculus 9Sp lamina 9 of the spinal gray BIC nucleus of the brachium of the inferior colliculus 10N nucleus BL basolateral amydaloid nucleus 10Ca dorsal motor nucleus of vagus, caudal part Bo Botzinger complex 10CaI dorsal motor nucleus of vagus, caudointermediate part bsc brachium of the superior colliculus 10CeI dorsal motor nucleus of vagus, centrointermediate part CA1 field CA1 of the 10DI dorsal motor nucleus of vagus, dorsointermediate part CA3 field CA3 of the hippocampus 10DR dorsal motor nucleus of vagus, dorsorostral part CAT central nucleus of the acoustic tract 10F dorsal motor nucleus of vagus, medial fringe Cb cerebellum 10n vagus nerve cbu 10RI, dorsal motor nucleus of vagus, rostrointermediate part CC 10Sp lamina 10 of the spinal gray CDPMn caudal dorsal paramedian nucleus 10Tr vagal trigone CeCv central cervical nucleus of the spinal cord 10VI dorsal motor nucleus of vagus, ventrointermediate part CeMe central mesencephalic nucleus 10VR dorsal motor nucleus of vagus, ventrorostral part CGPn central gray of the rhombencephalon 11n vagus nerve chp chorioid plexus 11N nucleus CIC central nucleus of the inferior colliculus 12N hypoglossal nucleus CIF compact interfascicular nucleus 12GH hypoglossal nucleus, geniohyoid part CLiAz caudal linear nucleus of the raphe, azygoz part 12L hypoglossal nucleus, lateral part CLiZ caudal linear nucleus of the raphe, zygoz part 12M hypoglossal nucleus, medial part CnF cuneiform nucleus 12n cp cerebral peduncle 12V hypoglossal nucleus, ventral part csp 12VL hypoglossal nucleus, ventrolateral part Crb cribiform nucleus

III. BRAINSTEM AND CEREBELLUM 264 8. ORGANIZATION OF BRAINSTEM NUCLEI csc commissure of the superior colliculus EVe nucleus of origin of vestibular efferents of the Ct conterminal nucleus EW Edinger-Westphal nucleus ctg central tegmental tract fr fasciculus retroflexus cu cuneate fasciculus fpn frontopontine fibers Cu cuneate nucleus FVe F-cell group of the vestibular complex CuR cuneate nucleus, rotundus part Gam gamma pontine nucleus CuT cuneate nucleus, triangular part g7 genu of the facial nerve Cx cerebral Gi gigantocellular reticular nucleus das dorsal acoustic stria GiV gigantocellular reticular nucleus, ventral part DA8 dopamine cells A8 GiA gigantocellular reticular nucleus, alpha part DC Gr gracile nucleus DCIC dorsal cortex of the inferior colliculus gr gracile fasciculus DG dentate GrC granular cell layer of cochlear nuclei Dk nucleus of Darkschewitsch hio hilus of the inferior olive dlf dorsal longitudinal fasciculus I3 interoculomotor nucleus DLG dorsal lateral geniculate nucleus I5 intertrigeminal nucleus DLL dorsal nucleus of the I8 interstitial nucleus of the vestibulocochlear nerve DLPAG dorsolateral periaqueductal gray ia internal arcuate fibers DMPAG dorsomedial periaqueductal gray icp inferior (restiform body) DM5 dorsomedial spinal trigeminal nucleus icv inferior cerebellar vein DMSp5 dorsomedial spinal trigeminal nucleus IF interfascicular nucleus dms dorsomedian IFH interfascicular hypoglossal nucleus dpms dorsal paramedian sulcus II intermediate interstitial nucleus of the medial DMTg dorsomedial tegmental area longitudinal fasciculus DpG deep gray layer of the superior colliculus ILL intermediate nucleus of the lateral lemniscus DPGi dorsal paragigantocellular nucleus IMLF interstitial nucleus of the medial longitudinal fasciculus DPO dorsal periolivary nucleus In intercalated nucleus DpWh deep white layer of the superior colliculus InC interstitial nucleus of Cajal DR dorsal raphe nucleus InCSh interstitial nucleus of Cajal, shell DRC dorsal raphe nucleus, caudal part InG intermediate gray layer of the superior colliculus DRD dorsal raphe nucleus, dorsal part InWh intermediate white layer of the superior colliculus DRI dorsal raphe nucleus, interfascicular part IO inferior olive DRL dorsal raphe nucleus, lateral part IOA inferior olive, subnucleus A of medial nucleus DRV dorsal raphe nucleus, ventral part IOB inferior olive, subnucleus B of medial nucleus dsc dorsal IoBe inferior olive, beta subnucleus dtg dorsal tegmental bundle IOC inferior olive, subnucleus C of medial nucleus DTgC dorsal tegmental nucleus, central part IOD inferior olive, dorsal nucleus DTgP dorsal tegmental nucleus, pericentral part IODC inferior olive, dorsal nucleus, caudal part E and subependymal layer IODM inferior olive, dorsomedial cell group EC epicoeruleus nucleus IOK inferior olive, cap of Kooy of the medial nucleus ECIC external cortex of the inferior colliculus IOM inferior olive, medial nucleus ECu external cuneate nucleus IOPr inferior olive, principal nucleus EF epifascicular nucleus IOVL inferior olive, ventrolateral protrusion EL endolemniscal nucleus IP interpeduncular nucleus

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 265

IPA interpeduncular nucleus, apical subnucleus m5 motor root of the IPC interpeduncular nucleus, caudal subnucleus MA3 medial accessory oculomotor nucleus IPDM interpeduncular nucleus, dorsomedial subnucleus MB IPF MdD medullary reticular nucleus, dorsal part IPI interpeduncular nucleus, intermediate subnucleus mdosa median dorsal spinal artery (branch of radicular) IPL interpeduncular nucleus, lateral subnucleus MdV medullary reticular nucleus, ventral part IPo interpositus mcp middle cerebellar peduncle IPR interpeduncular nucleus, rostral subnucleus MCPC magnocellular nucleus of the ipt interpedunculotegmental tract Me5 mesencephalic trigeminal nucleus IRt intermediate reticular nucleus me5 mesencephalic trigeminal tract IS inferior salivatory nucleus MeF dorsal motor nucleus of vagus, medial fringe isRt isthmic reticular formation MG medial geniculate nucleus jx juxtarestiform body MGD medial geniculate nucleus, dorsal part JxO juxtaolivary nucleus MGM medial geniculate nucleus, medial part KF Ko¨llikereFuse nucleus MGV medial geniculate nucleus, ventral part LC locus coeruleus MiTg microcellular tegmental nucleus lcs lateral corticospinal tract ml LDTg laterodorsal tegmental nucleus ML medial mammillary nucleus, lateral part LDTgV laterodorsal tegmental nucleus, ventral part mlf medial longitudinal fasciculus lf lateral MnR lfp longitudinal fibers of the Mo5 motor trigeminal nucleus Li linear nucleus of the hindbrain mp mammillary peduncle ll lateral lemniscus MPB medial parabrachial nucleus LPAG lateral periaqueductal gray MPBE medial parabrachial nucleus, external part LPB lateral parabrachial nucleus MPCu medial pericuneate nucleus LPBC lateral parabrachial nucleus, central part mRt mesencephalic reticular formation LPBD lateral parabrachial nucleus, dorsal part mscb middle superior cerebellar artery LPBE lateral parabrachial nucleus, external part MSO medial superior olive LPBS lateral parabrachial nucleus, superior part mtg mammillotegmental tract LPCu lateral pericuneate nucleus MVe medial vestibular nucleus LPGi lateral paragigantocellular nucleus MVeMC medial vestibular nucleus, magnocellular part LR4V of the 4th ventricle MVePC medial vestibular nucleus, parvicellular part LRt lateral reticular nucleus MVPO medioventral periolivary nucleus LRtPC lateral reticular nucleus, parvicellular part Mx matrix region of the rhombencephalon LRtS5 lateral reticular nucleus, subtrigeminal part MZMG marginal zone of the medial geniculate nucleus lscb lateral superior cerebellar artery (branch of superior NA1 noradrenaline cells A1 cerebellar) NA1/Ad1 noradrenaline cells A1 and/or adrenaline cells C1 LSO lateral superior olive NA2 noradrenaline cells A2 LT lateral terminal nucleus of the accessory NA2/Ad2 noradrenaline cells and/or adrenaline cells C2 Lth lithoid nucleus NA5 noradrenaline cells A5 LV lateral ventricle NA7 noradrenaline cells A7 LVe lateral vestibular nucleus Nt noto cuneate nucleus LVPO lateroventral periolivary nucleus oc lvs lateral ocb olivocochlear bundle

III. BRAINSTEM AND CEREBELLUM 266 8. ORGANIZATION OF BRAINSTEM NUCLEI ocpn occipitopontine fibers pos preolivary sulcus ODPMn oral dorsal paramedian nucleus PoT posterior thalamic nuclear group, triangular part Op layer of the superior colliculus PP peripeduncular nucleus opt optic tract PTg pedunculotegmental nucleus p1PAG p1 periaqueductal gray Pr prepositus nucleus p1Rt p1 reticular formation Pr5 principal sensory trigeminal nucleus Pa4 paratrochlear nucleus PrEW pre-Edinger-Westhpal nucleus P5 peritrigeminal zone PrBo pre-Botzinger complex P7 perifacial zone PrC precommissural nucleus Pa5 paratrigeminal nucleus PrCnF precuneiform area Pa6 paraabducens nucleus PSol parasolitary nucleus PaP parapeduncular nucleus psp PaRa pararaphales nucleus ptpn parietal pontine fibers PaS Pul PaVe paravestibular nucleus PVM posterior ventromedial thalamic nucleus PBG prabigeminal nucleus py pyramidal tract PBP parabrachial pigmented nucleus of the ventral tegmental pyx pyramidal area RAmb retroambiguus nucleus pc posterior commissure Rbd rhabdoid nucleus PC3 parvicellular oculomotor nucleus RC raphe cap PCom nucleus of the posterior commiddure RIP raphe interpositus nucleus PCRt parvicellular reticular nucleus RIs retroisthmic nucleus PCRtA parvicellular reticular nucleus, alpha part RLi rostral linear nucleus PCuMx pericuneate matrix RM retromamillary nucleus PDR posterodorsal raphe nucleus RMC red nucleus, magnocellular part PDTg posterodorsal tegmental nucleus RMg raphe magnus nucleus PIF parainterfascicular nucleus Ro nucleus of Roller Pe5 peritrigeminal nucleus ROb raphe obscurus nucleus PF parafascicular thalamic nucleus RPa raphe pallidus nucleus pica posterior inferior cerebellar artery RPC red nucleus, parvicellular part PIL posterior intralaminar thalamic nucleus RPF retroparafascicular nucleus PlGl pleioglia periaqueductal gray RPn raphe pontis nucleus PLi limitans thalamic nucleus, posterior part RRF retrorubal field pm principal mammillary tract rs PMnR paramedian raphe nucleus RtTg reticulotegmental nucleus PN paranigral nucleus of RtTgL reticulotegmental nucleus, lateral part Pn pontine nuclei RTz retrotrapezoid nucleus PnB pontobulbar nucleus RVL rostroventrolateral reticular nucleus of the PnC pontine reticular nucleus, caudal part rhombencephalon PnO pontine reticular nucleus, oral part RVRG rostral ventral respiratory group Po posterior thalamic nuclear group S PoDG polymorph layer of the s5 sensory root of the trigeminal nerve pof post-olivary fissure Sag sagulum nucleus pola paraolivary artery SC superior colliculus polv paraolivary vein scol supracollicular arterial network

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 267 scp superior cerebellar peduncle SubCD subcoeruleus nucleus, dorsal part scpd superior cerebellar peduncle, descending limb SubCV subcoeruleus nucleus, ventral part SG suprageniculate thalamic nucleus SuG superficial gray layer of the superior colliculus SGe supragenual nucleus SuL supralemniscal nucleus sl SuM supramammillary nucleus smv SuVe superior vestibular nucleus SNC substantia nigra, compact part tepn temporopontine fibers SNCD substantia nigra, compact part, dorsal tier tfp transverse fibers of the pons SNCM substantia nigra, compact part, medial tier ts SNCV substantia nigra, compact part, ventral tier tth trigeminothalamic tract () SND substantia nigra, dorsal part Tz nucleus of the SNL substantia nigra, lateral part tz trapezoid body SNR substantia nigra, reticular part U nucleus U SNV substantia nigra, ventral part vcs ventral corticospinal tract Sol solitary nucleus VCP , posterior part sol veme vestibulomesencephalic tract SolC solitary nucleus, commissural part vfu ventral funiculus SolD solitary nucleus, dorsal part VH ventral horn SolDL solitary nucleus, dorsolateral part VLL ventral nucleus of the lateral lemniscus SolG solitary nucleus, gelatinous part vlmv ventrolateral medullary vein SolI solitary nucleus, interstitial part vls ventrolateral sulcus SolIM solitary nucleus, intermediate part VLPAG ventrolateral periaqueductal gray SolM solitary nucleus, medial part VLTg ventrolateral tegmental area SolPaC solitary nucleus, paracommissural part vmf ventral median fissure SolV solitary nucleus, ventral part VPI ventral posterior inferior nucleus SolVL solitary nucleus, ventrolateral part VPM ventral posteromedial thalamic nucleus Sp5 spinal trigeminal nucleus vcs ventral corticospinal tract sp5 spinal trigeminal tract vr ventral root Sp5C spinal trigeminal nucleus, caudal part vsc ventral spinocerebellar tract Sp5C1 spinal trigeminal nucleus, caudal part, lamina 1 vspa ventral spinal artery (branch of vertebral, radicular) Sp5C2 spinal trigeminal nucleus, caudal part, lamina 2 VTA ventral tegmental area Sp5C3/4 spinal trigeminal nucleus, caudal part, lamina 3/4 VTAR ventral tegmental area, rostral part Sp5I spinal trigeminal nucleus, interpolar part vtg ventral tegmental tract Sp5O spinal trigeminal nucleus, oral part VTg ventral tegmental nucleus (Gudden) SPO superior paraolivary nucleus vtgx ventral tegmental decussation SPP subpeduncular pigmented nucleus X nucleus X spth x4 n decussation of the trochlear nerve SpVe spinal vestibular nucleus xml decussation of the medial lemniscus STh xscp decussation of the superior cerebellar peduncle Su3 supraoculomotor perieaqueductal gray Y nucleus Y Su3C supraoculomotor cap Z nucleus Z Su5 supratrigeminal nucleus ZI SubB subbrachial nucleus Zo zonal layer of the superior colliculus SubC subcoeruleus nucleus

III. BRAINSTEM AND CEREBELLUM 268 8. ORGANIZATION OF BRAINSTEM NUCLEI

dms –2 mdosa dpms –3 dpms

–3 Gr Gr

–4 cu gr gr –4 cu Sp5C1 –5 sp5 Sp5C2 Sp5C1 –5 Sp5C2 sp5 Sp5C2 Sp5C2 Sp5C3/4 –6 Sp5C3/4 5Sp IB IB –6 5Sp

dsc CeCv –7 7Sp dsc rs –7 rs CeCv –8 CC lcs 10Sp CeCv –8 CC E lcs 10Sp spth –9 E RAmb –9 RAmb vsc spth –10 8Sp mlf vr –10 pyx vsc 8Sp ts 9Sp lfu lfu –11 mlf vcs –11 vmf 9Sp lvs ts –12 vfu -16 mm vmf –12 vspa vfu lvs vcs Obex -15 mm 012345 asp –13 FIGURE 8.1 - 012345 FIGURE 8.2 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 269

dms mdosa –2 –2 dpms dms dpms gr Gr –3 Gr –3 gr cu cu –4 –4 Sp5C2 Sp5C1 sp5 Sp5C2 –5 –5 sp5 Sp5C1 Sp5C2 Sp5C2 Cu Sp5C3/4 Sp5C3/4 –6 IB 5Sp –6 Nt Au CeCv MdD –7 dsc rs –7 CeCv CeCv dsc 10Sp 10Sp rs CC –8 –8 E lcs lfu E CC lcs

–9 RAmb spth –9 RAmb

pyx spth –10 vsc MdV VH –10 pyx

8Sp –11 mlf lfu vsc –11 8Sp ts 9Sp vls –12 9Sp mlf vcs –12 vls lvs vmf vfu Obex -14 mm lvs –13 asp ts

–13 vcs vfu 012345 Obex -13 mm FIGURE 8.3 - vmf asp –14 012345

FIGURE 8.4 -

III. BRAINSTEM AND CEREBELLUM 270 8. ORGANIZATION OF BRAINSTEM NUCLEI

dms –1 dms dpms –2 psp dpms gr gr –2 Gr –3 cu Gr –3

psp –4 cu Sp5C1 Sp5C1 –4 Sp5C2

–5 Nt sp5 Cu sp5 Nt Sp5C2 –5 Sp5C2 Au Nt Cu Sp5C3/4 –6 Au CeCv Sp5C3/4 –6 CeCv 10Sp lcs CeCv –7 CC 10Sp E MdD rs dsc CC –7 MdD IRt lcs rs dsc –8 lcsp E IRt –8 RAmb RAmb –9 NA1 MdV pyx lcsp NA1 –9 spth spth –10 MdV

lfu vsc –10 lfu pyx –11 mlf 9Sp –11 ts mlf vls 9Sp vsc –12 ts lvs vfu vls –12 lvs –13 vcs vmf Obex -12 mm vfu –13 Obex -11 mm asp vcs –14 012345 vmf –14 - FIGURE 8-5 0123456

FIGURE 8-6 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 271

0 dms mdosa –1 dms gr dpms dpms –1 gr

–2 Gr

–2 Gr –3 cu cu psp Sp5C1 –3 –4 Nt Cu Au sp5 –4 Nt Cu Sp5C1 Sp5C2 –5 Au sp5 Sp5C3/4 10Sp CeCv –5 Sp5C2 psp 10Sp –6 CC Sp5C3/4 CeCv CeCv CC E MdD –6 E rs dsc –7 lcs MdD IRt –7 rs dsc lcs –8 IRt RAmb NA1 –8 RAmb MdV NA1 –9 pyx spth MdV spth lfu –9 –10 vsc pyx 9Sp mlf –10 9Sp –11 mlf ts vsc lvs –11 ts –12 lvs vfu –12 vfu –13 Obex -10 mm vcs vmf –13 py –14 Obex -9 mm 012 34 56 vmf –14 FIGURE 8.7 - 0123456

FIGURE 8.8 -

III. BRAINSTEM AND CEREBELLUM 272 8. ORGANIZATION OF BRAINSTEM NUCLEI

0 mdosa mdosa dms 0 dms –1 gr dpms gr dpms –1 Gr –2 Gr psp psp cu –2 cu –3

Sp5C1 Cu –3 Cu –4 Au Sp5C1 Sp5C2 sp5 –4 –5 Sp5C2 NA2 CeCv Sp5C3/4 CeCv 10Sp 10Sp sp5 –5 ia CC CC Sp5C3/4 –6 E CeCv CeCv MdD E –6 rs dsc MdD –7 IRt xml ia dsc –7 IRt rs RAmb –8 NA1/Ad1 MdV AmbL –8 spth MdV –9 mlf mlf 9Sp NA1/Ad1 9Sp –9 spth –10 pyx pyx vsc ts ts –10 vsc –11 lvs –11 lvs –12

–12 –13 py Obex -8 mm –13 py –14 Obex -7 mm 0123456 –14 FIGURE 8.9 - 01234567

FIGURE 8.10 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 273

dms 1 0 dms gr gr dpms dpms 0 pica –1

Gr –1 Gr –2 cu

cu –2 –3

Cu –3 Cu Sp5C1 SolPaC pica –4 Mx

SolC Sp5C1 sp5 –4 Mx –5 NA2 NA2 CC 10Ca sp5 ia Sp5C3/4 CC E CeCv Sp5C2 Sp5C2 –5 Sp5C3/4 –6 CeCv E MdD 11n IRt –6 –7 ia 11n AmbL MdD rs ia IRt rs dsc dsc –7 –8 NA1/Ad1 mlf MdV mlf 9Sp ml 9Sp AmbL –8 –9 spth MdV RVRG NA1/Ad1

–9 spth –10 pyx vsc ts ts LRt vsc lvs –10 pyx –11

–11 –12 pyx 12n –12 –13 py py –13 –14 Obex -6 mm Obex -5 mm

–14 01234567 01234567 FIGURE 8.11 - FIGURE 8.12 -

III. BRAINSTEM AND CEREBELLUM 274 8. ORGANIZATION OF BRAINSTEM NUCLEI

dms 2 1 pica dms gr 1 0 gr pica

Gr Gr –1 0 cu cu icp –2 –1 ECu pica SolPaC Cu ECu CuT SolPaC –2 –3 Cu CuR LPCu Sp5C1 ECu SolIM SolC –3 SolC –4 NA2 Mx Mx 10Ca sp5 10Ca CC NA2 CeCv Sp5C3/4 sol Sp5C2 sp5 –5 Sp5C2 –4 E In E ia CC 12N Sp5C3/4 ia MdD 12N CeCv –6 –5 IRt 12GH MdD Sp5C1 rs pica dsc ia IRt –7 –6 rs ia mlf AmbL RVRG mlf AmbL MdV NA1/Ad1 9Sp –8 9Sp –7 ts RVRG ml ts spth MdV spth ia NA1/Ad1 IOK vsc –8 pica –9 IOK vsc LRt ml IOBe LRt –10 –9 12n –10 –11 IOA

py py –12 –11

–13 –12 Obex -3 mm Obex -4 mm –14 –13 012345678 01234567 FIGURE 8.14 - FIGURE 8.13 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 275

2 2 pica dms dms gr 1 gr 1 Gr Gr 0 0 ECu cu cu SolG –1 –1 SolM SolPaC ECu SolPaC Cu CC CuT CuT CuR Mx ECu –2 SolC Cu pica –2 CuR ECu SolC 10Ca icp icp sol pica NA2 SolV E In LPCu –3 Mx LPCu –3 SolVL CC 10Ca cu 12L ia sp5 sol Pe5 SolIM E NA2 Sp5C Cu –4 12M Pe5 –4 Sp5C2 In SolIM ia Sp5C3/4 Sp5C1 12GH 12M sp5 Sp5I –5 MdD –5 MdD IRt mlf dsc 12GH rs IRt ROb mlf –6 –6 rs MdV AmbL AmbL LRtS5 dsc ts LRtS5 ROb RVRG MdV spth –7 –7 ia ts NA1/Ad1 NA1/Ad1 vsc ia IOK Li –8 IOK spth –8 vsc 12n LRt IOD LRt –9 –9 ml IOBe IOBe 12n IOD ml IOC –10 –10 IOB vlmv IOB IOPr IOA IOA –11 –11 pola Ct py Ct py vlmv –12 –12 Obex -1 mm

Obex -2 mm –13 01234567 8 FIGURE 8.16 - 01234567 8

FIGURE 8.15 -

III. BRAINSTEM AND CEREBELLUM 276 8. ORGANIZATION OF BRAINSTEM NUCLEI

2 2

gr gr ECu 1 1 4V Gr Gr NA2 AP cu SolG cu SolG PSol 0 AP 0 ECu SolPaC 10CeI SolPaC SolM SolDL –1 SolDL CuR CuR SolM –1 10CaI icp SolC SolV Mx SolI cu 10CaI sol 10F sol –2 10F ECu –2 ECu SolVL In In E SolIM MPCu E MPCu LPCu NA2 cu LPCu SolVL Mx –3 SolIM 12L 12L SolV icp –3 DM5 DM5 Pa5 12M vtg 12M –4 sp5 –4 ia 12V 12V Sp5I sp5 MdD Sp5I pica MdD mlf –5 dsc –5 mlf dsc IRt pica rs ROb MdV rs MdV AmbL IRt –6 LRtS5 –6 LRtS5 RVRG ROb AmbSC NA1/Ad1 ts vsc –7 ts –7 RVRG ia vsc ia NA1/Ad1 spth IOK Li spth Li IOD –8 –8 IOD LRt IOK LRt EL –9 ml 12n IOVL –9 Ct pof IOBe IOVL ctg pof ml ami IOBe polv –10 IOC ctg polv ami –10 IOPr IOB IOPr IOB RPa IOC –11 IOA OC –11 IOA oc py RPa Ct –12 –12 Obex 0 mm Ct 12n

–13 pos 01234567 8 py FIGURE 8.17 - –14

–15 Obex +1 mm

–16

0123456789

FIGURE 8.18 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 277

2 2 LR4V 4V 4V Gr Z AP Z 1 SolG 1 PSol Cu SolG PSol cu E cu SolM 0 SolDL 0 SolM 10DI 10CeISolDL Cu 10CeI SolV 10DI 10F SolV –1 10VI ECu SolI In sol SolI –1 10F Mx cu E cu SolVL 10CaI NA2/Ad2SolIM icp sol ECu cu In NA2 –2 12L –2 MPCu Mx SolVL 12M 12L SolIM Mx LPCu MPCu DM5 –3 –3 12M vtg 10n LPCu ia 12V ia Pa5 Pa5 Pe5 icp –4 –4 12V Sp5I Sp5I MdD sp5 mlf MdD sp5 mlf dsc –5 MdV IRt –5 ia MdV IRt ROb pica ROb rs –6 –6 dsc rs ts Pe5 LRtS5 10n AmbSC LRtS5 pica ts IOM Pe5 –7 –7 RVRG Ad1 IOM Li AmbSC LRt Pe5 ia Li vsc spth RVRG vsc LRt spth –8 –8 IOD Ad1 IOD Ct pola 12n Ct ctg polv –9 –9 ami ctg pof pof EL pola IOM IOPr ami –10 EL 12n polv –10 hio ml ml IOBe pola IOM –11 IOM –11 IOPr oc RPa oc

–12 –12 Ct Ct RPa –13 –13

py pos –14 py pos –14

–15 –15 Ar Ar Obex +2 mm –16 Obex +3 mm –16

0123456789 0123456789

FIGURE 8.19 - FIGURE 8.20 -

III. BRAINSTEM AND CEREBELLUM 278 8. ORGANIZATION OF BRAINSTEM NUCLEI

2 2 Cb PnB PnB SolDL 1 1 4V MVe 4V PSol cu SolG Mx Mx SolM PSol Cu SolG MPCu cu SolM SpVe 0 SolDL 0 sl 10DI 10CeI SolV SpVe sl 10DI SolV 10CeI Crb 10F 10F SolI –1 sol SolI –1 E In sol Crb E 10VI ECu ECu In icp NA2/Ad2 10VI SolVL –2 NA2/Ad2 –2 SolIM SolIM 12N LPCu 12N SolVL MPCu MPCu Mx Mx cu –3 icp –3 Ro Ro LPCu 10n mlf PMnRt LPCu –4 PCRt sp5 –4 Pe5 PCRt Sp5I mlf Sp5I chp Pa5 Pa5 Gi sp5 –5 ROb IRt –5 Gi ROb dsc ts IRt –6 ts Pe5 –6 GiV Li chp AmbSC Pe5 Pe5 dsc rs 10n Li pica LPGi rs LRtS5 –7 –7 AmbSC pica Pe5 spth LPGi LRtS5 RVRG IOD vsc IOD RVRG vsc Ad1 LRt –8 spth EL 12n Ad1 –8 LRt 12n ami Ct –9 EL pola –9 Ct polv

pof pof –10 ctg ctg –10 ami polv ml IOM

–11 ml IOM –11 EL IOPr EL oc oc –12 RPa RPa –12 Ct IOPr

–13 Ct –13

–14 –14 RPa py py pos pos –15 –15

–16 Obex +4 mm –16 Obex +5 mm –17 –17 0123456789 0123456789 FIGURE 8.21 - FIGURE 8.22 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 279

2 2

chp Cb chp Chp Cb 1 MVe 1 MVe 4V SolM SolG Cb 10Tr PaVe MeF SolDL SpVe 4V sl 10DI SolG sl SolD SolD Mx 10DI PCuMx 0 SolM SpVe 0 E In 10VI SolDL PSol MeF PnB E In SolV SolV –1 10CeI chp sol –1 10CeI Crb ECu sol ECu 12N SolI SolI 10VI Ad2 Crb icp –2 12N SolIM –2 SolIM SolVL MPCu icp NA2/Ad2 cu Ro 12n SolVL mlf oc MPCu –3 DPGi PMnRt Mx PMnRt –3 Ro 10n 10n oc –4 IRt PCRt mlf DPGi Pa5 Sp5I –4 PCRt oc sp5 Gi –5 Sp5I sp5 ROb oc sp5 Pe5 oc –5 AmbC oc Gi sp5 ts GiV sp5 –6 LR4V 12n PrBo Pe5 12n IRt Pe5 Pe5 rs –6 ts GiV oc 10n LPGi rs –7 IOD LRt LPGi spth vsc ROb Pe5 LRtS5 pica LR4V –7 LRtS5 Pe5 AmbSC –8 Ad1 IOD LRt vsc LRt RVRG spth –8 EL pica –9 10n IOPr pof LRt Ad1 IODM ami ctg

–9 IOM –10 ami pof IODM ctg –11 ml 12n oc –10 ml

EL –12 IOM –11 EL IOPr EL 12n oc –13 –12 RPa EL Ct –14 RPa –13 RPa pos RPa –15 py –14 –16 py –15 pos –17 Obex +7 mm

–16 Obex +6 mm 01234567899 10 –17 FIGURE 8.24 -

012345678910

FIGURE 8.23 -

III. BRAINSTEM AND CEREBELLUM 280 8. ORGANIZATION OF BRAINSTEM NUCLEI

2 2 Cb PaVe chp Cb Cb PaVe MVe 1 MVe 1 sl 10RI Mx PnB 4V SolDL IPo sl SpVe 0 4V SpVe 0 SolM SolM 10DR SolD X E MeF Pr SolIM MeF SolI –1 Pr 10DR SolI CDPMn SolIM sol –1 10VR PnB 12N sol 5Sol X 10VR Ad2 ECu EF Ad2 mlf –2 Ro 10n Crb icp –2 10n icp mlf SolVL oc DPGi 5Sol DM5 oc DPGi –3 DM5 –3 PCRt PCRt IRt PMnRt Sp5I ts –4 –4 Sp5I AmbC Gi sp5 sp5 sp5 Gi ROb –5 AmbC –5 oc ts LR4V GiV PrBo GiV –6 –6 PnB Pe5 Pe5 Bo chp LRtS5 rs Pe5 IRt LRtS5 ROb IOD IOD rs sp5 10n –7 vsc –7 LPGi spth pica LPGi Ad1 Ad1 vsc –8 10n Pe5 pica LRt –8 IODM ami spth JxO JxO IODM –9 pof –9 pof ami LR4V ctg ctg IOM –10 –10 PnB chp 12n ami IOM –11 –11 ml oc ml EL IOPr –12 IOPr –12 oc EL EL –13 –13 RPa RPa Ct RPa –14 RPa –14 Ct py –15 py –15 pos pos Obex +9 mm –16 –16 Obex +8 mm 012345678910 11 –17 FIGURE 8.26 - 012345678910 11

FIGURE 8.25 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 281

2 3 SubV das Cb Y SGl Cb Y 1 4V E das 2 E MVe SpVe DC das IPo 4V 0 1 DC IPo MVe jx Pr FVe 10DR CDPMn SolIM CDPMn –1 0 SpVe EF EF Pr Ad2 SolI sol 10DR mlf 10VR mlf –2 X –1 sol DPGi 5Sol 9n oc icp icp DPGi SolI 10VR DM5 5Sol 9n –3 –2 SolIM oc DM5 PCRt IRt Sp5I –4 –3 IRt 9n oc PCRt VCP Gi Sp5I –5 sp5 –4 ROb PnB oc ROb Gi AmbC PnB sp5 –6 ts –5 AmbC GiV Bo oc –7 LRtS5 rs –6 Bo PnB rs LRtS5 IOD LPGi IRt vsc 9n ts vsc spth 9n –8 –7 IOD spth Ad1 LPGi Ad1 JxO pica RVL –9 IODM –8 IOD ami JxO pof LR4V ctg pof –10 ami –9 IODM chp IODM –11 –10

ml RPa –12 oc –11 IOPr IOPr ml RPa oc –13 –12

–14 EL –13

–15 –14 py py pos Obex +10 mm Obex +11 mm –16 –15

012345678910 11 12 012345678910 11 12

FIGURE 8.27 - FIGURE 8.28 -

III. BRAINSTEM AND CEREBELLUM 282 8. ORGANIZATION OF BRAINSTEM NUCLEI

4 5 Y SuVe chp 3 chp 4 Cb SuVe Cb LVe Y PnB mcp 2 E 3 4V 4V MVe jx das LVe 1 IPo 2 CDPMn E mcp Pr icp MVePC EF SpVe IPo 0 1 Pr icp EF jx mlf sol mlf –1 DPGi SolI 0 IS GrC MVeMC sol DPGi 5Sol SpVe –2 –1 SolI oc DM5 IS 5Sol GrC –3 oc –2 ROb PCRt Sp5I Gi VCP ts ROb PCRt Sp5I AVC –4 sp5 –3 Gi sp5 –5 ts IRt –4 IRt

RMg rs –6 PnB PnB –5 IOD 8n RMg vsc GiA rs –7 LPGi –6 RTz 9n vsc IOD spth LPGi –8 –7 IOD spth PnB ami pof PaRa IODM ctg –9 –8 ctg

ami –10 –9 RPa

–11 RPa oc –10 IOPr IOPr –12 –11 ml oc ml –13 –12

–14 py –13 py Obex +13 mm Obex +12 mm –15 –14 012345678910 11 12 13 0 1 234567 8 9 10 11 12 13 FIGURE 8.30 - FIGURE 8.29 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 283

Cb 5 5 SuVe SuVe 4V chp mcp 4 4 4V E MVePC jx 7n icp 3 3 icp jx PnB g7 LVe E MVePC 6N MVeMC

Pr 2 mlf 2 LVe I8 ODPMn 6N MVeMC 1 Pa6 SolI 1 Pa6 sol mlf SolI oc PCRt SpVe DPGi IRt 0 RPn 0 DPGi asc7 8vn IS sol Sp5O ts 7SH –1 –1 I8 sp5 I8 ts IRt PCRt Gia 7DM –2 Sp5O –2 8n 7SH 7DI 7L 7DM AVC –3 7VM –3 Gi sp5 mcp 7VI 7VL tz I8 P7 rs 7DI 7L –4 GiA NA5 LSO –4 RMg SOl 7VM tz LVPO 7VL ocb vsc 7n 7VI rs ctg –5 MSO –5 RMg P7 spth GiA SPO MVPO LPGi –6 –6 RTz vsc PnB mcp spth –7 7n –7 ml

–8 –8 IOPr ctg PnB ami –9 Pn –9 IOPr Pn Obex +15 mm oc 7n –10 –10 mcp ml 01234567 8 9 10

–11 FIGURE 8.32 -

–12 py Obex +14 mm –13

0 1 234567 8 9 10 11 12 13

FIGURE 8.31 -

III. BRAINSTEM AND CEREBELLUM 284 8. ORGANIZATION OF BRAINSTEM NUCLEI

8 6 4V 7 jx 5 4V SuVe icp icp Gam E 6 SuVe SGe 4 MVePC g7 EVe jx 5 MVeMC SGe E LVe CGPn 3 6N veme mcp mlf EVe Gam I8 4 g7 7n 7n sol 2 veme sol Pa6 SolI ocb 6N 3 mlf SolI 5N PCRtA Pa6 PCRtA I8 SubCD 1 RPn Gam Pr5 PnC Sp5O mcp P5 sp5 2 5N PCRtA 8vn IRt 8vn 0 ts 7DM Pr5 –1 PCRtA Sp5O –1 7N RPn PnC Gi Sp5O RIP sp5 7VL –0 SubCV –2 6n tz 7N P7 ts Sp5O –1 P7 GiA NA5 LSO ctg ctg RTz SOl –3 NA5 tz RIP 6n LSO Gam 7n RMg –2 MSO vsc mcp tz –4 SPO tz vsc MVPO MSO spth –3 RMg SPO LVPO Tz –5 Tz Pn spth ml –4 RtTg MVPO –6 ml –5 –7 Obex +16 mm Obex +17 mm Pn tfp –6 01234567 8 9 0123456789 FIGURE 8.33 - FIGURE 8.34 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 285

9 9 icp MPB scp

SuVe scp 8 icp 8 Me5 4V Gam Gam mcp 4V MPB vsc mcp Gam Gam 7 Me5 7 CGPn SuVe E Gam SuVe veme Gam 5Tr Gam 6 6 Gam me5 E 5Tr Gam CGPn veme EVe Gam Gam me5 RtTgL Gam g7 5 5Te 5 SubCD I5 mlf DMTg Gam RtTgL Gam ocb 4 DMTg SubCD 4 5Pt Gam 5N Gam 5Ma Pr5 mlf I5 5MHy P5 m5 P5 3 Pr5 3 5ADi Gam RPn PnC RtTgL 5PC 2 PCRtA 2 PnC PCRtA s5 RPn SubCV m5 Sp5O ctg 1 1 ts Gam rs SubCV s5 ctg Gam ts RtTg NA5 0 0 vsc ll NA5 tz SuL tth CAT Gam –1 –1 RtTg tz rs MVPO SPO LVPO Tz vsc spth –2 –2 ml MSO Gam RtTg Tz MVPO spth –3 ml –3 Obex +19 mm

Pn –4 Obex +18 mm 01234567 8 9 Pn FIGURE 8.36 - 01234567 8 9 10

FIGURE 8.35 -

III. BRAINSTEM AND CEREBELLUM 286 8. ORGANIZATION OF BRAINSTEM NUCLEI

11 11 10 scp 10 Cb scp 9 4V 9 Me5 4V Cb 8 Gam Me5 8 Gam me5 Gam CGPn LC mcp 7 E E CGPn veme 7 LC MPB Gam Su5 veme 6 PDTg Gam RtTgL Gam MPB 5Tr SubCD 6 5Te Su5 mlf vsc SubCD vsc mlf 5 DRC DMTg Gam DRC DMTg 5Tr I5 5 P5 5Pt 5Ma 4 Pr5 P5 5N RtTgL 4 Gam mcp SubCV 5PC 3 RtTgL PnO PnO ctg 5PC 3 m5 PMnR ctg Gam m5 2 VLTg vsc VLTg 5PC ts ts 2 Pn RtTg 1 SuL NA5 RtTg NA5 Gam m5 ll s5 Pn tth Gam vsc 1 tth SuL ll CAT Gam SuL CAT 0 RtTg mcp RtTg B9 m5 m5 ml 0 ml MVPO spth –1 spth Pn –1 mcp –2 Obex +20 mm –2 m5 Pn Pn –3 tfp Obex +21 mm 01234567 8 9 –3

FIGURE 8.37 - 0123456789 FIGURE 8.38 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 287

12 12

11 11 scp Cb 10 scp 10 Cb

Me5 9 9 4V EC Me5 4V me5 me5 CGPn E LC 8 CGPn 8 MPB E LC PDTg MPB SubCD 7 7 SubCD DRC PDTg veme RtTgL Cb 6 mlf LPBE DRC DMTg Gam 6 Gam MPBE mlf MPBE mcp mcp RtTgL KF 5 LPBE 5 PnO RtTgL Pn ctg vsc Gam vsc Pn PMnR PnO 4 4 PMnR NA7 ts VLTg ctg Gam ll Pn rs 3 3 m5 m5 B9 tth mcp CAT Pn VLTg rs Pn RtTg SuL ll 2 ts 2 spth mcp tth CAT Pn ml 1 RtTg B9 SuL 1

spth ml Pn m5 0 0 Pn m5 tfp –1 Pn –1 tfp

–2 –2 tfp Pn Obex +23 mm

–3 tfp Obex +22 mm –3 01234567 8 9 01234567 8 9 FIGURE 8.40 - FIGURE 8.39 -

III. BRAINSTEM AND CEREBELLUM 288 8. ORGANIZATION OF BRAINSTEM NUCLEI

14 12

11 13 scp Cb Me5 10 12 Cb 4V EC 11 9 E CGPn me5 Cb

scp LC Cb 8 LDTg 10 SubCD Me5 PDTg EC 4V 9 E me5 7 RtTgL MPB DRC Bar mlf LC RtTgL mscb 8 LDTg LPBE 6 vsc CGPn MPBE KF MPB PnO ctg DRC 7 LPBE 5 PMnR mcp DRI Pn mlf 6 RtTgL 4 Gam mscb MPBE ts VLTg ll 5 3 CAT KF tth PMnR PnO ctg B9 mcp RtTg SuL 4 VLTg 2 ml spth ts Gam ll 1 3 CAT Pn Pn Pn tth B9 2 RtTg SuL spth 0 ml tfp 1 –1 Pn Pn Pn

tfp Obex +24 mm –2 0 Obex +25 mm 01234567 8 9 –1 01234567 8 9 10 FIGURE 8.41 - FIGURE 8.42 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 289

14 15

mscb 13 14

12 13

smv 11 12 EC

EC 4V E Cb Me5 Me5 10 11 CGPn LPB LC LPB me5 me5 scp CGPn 4V Bar scp LDTg 9 10 LC LDTg E DTgC Bar LC mscb LPBE 8 DTgC 9 LDTgV MPB LPBE DRC DTgP LDTgV MPB DTgP 7 mlf 8 DRC mlf mscb DRI mtg DRI KF KF 6 mtg RtTgL 7 ctg

ctg 5 6 MPBE PMnR PMnR VLL ll ll CAT PnO VLTg PnO mcp MnR 4 VLTg 5 ts spth mcp scpd ts spth scpd 3 4 B9 B9 ml B9 SuL B9 ml RtTg tth 2 3 SuL tth Pn

Pn 1 2 RtTg

Obex +26 mm tfp Obex +27 mm 0 1

01234567 8 9 10 01234567 8 9 10

FIGURE 8.43 - FIGURE 8.44 -

III. BRAINSTEM AND CEREBELLUM 290 8. ORGANIZATION OF BRAINSTEM NUCLEI

15 15

mscb 14 14 smv

smv 4V EC E LPBD 13 EC 13 Me5 me5 4V me5 E LPBD Me5 12 12 LDTg LC LC LPBC LDTg MPB 11 LPBC 11 DRC DTgP scp DRC DTgP 10 10 DTgC LDTgV MPB scp DTgC LDTgV 9 LPB 9 DRI LPB mlf mlf DRI 8 mtg 8 ll ctg mtg ctg KF 7 ll 7 VLL PnO MnR PMnR VLL 6 6 VLTg spth PnO VLTg MnR spth mcp PMnR mcp 5 5 ts tth tth ts scpd ml scpd 4 ml 4 Pn RtTg SuL SuL

B9 Pn 3 3 Pn B9

2 2 tfp tfp tfp 1 Obex +28 mm 1 Obex +29 mm

01234567 8 9 10 01234567 8 9 10 FIGURE 8.45 - FIGURE 8.46 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 291

15 smv 15 x4n smv 4n 4V Me5 RCme5 14 14 4V E E EC EC Me5 me5 LPBD LC 13 LDTg LC MPB 13 MPB LDTg DRC LPBD 12 mscb 12 LPBC mscb lscb DTgC PTg 11 11 DTgP LPB

LDTgV ll 10 10 DRC DTgC LDTgV DRI DTgP DRI mlf DLL DLL 9 9 mlf scp mtg mtg ILL ll scp 8 ctg 8 ctg ILL spth 7 7 spth VLTg PnO MnR RIs VLTg 6 mscb 6 PnO MnR 5 5 ts mcp ts ml PMnR ml 4 scpd tth 4 tth PMnR Pn 3 3 mcp

B9 Pn Pn 2 2 B9

1 tfp 1 lfp lfp tfp tfp tfp tfp 0 0 tfp lfp Obex +31 mm –1 –1 Obex +30 mm –2 0 1 234567 8 9 10 11 12

0 1 234567 8 9 10 11 12 FIGURE 8.48 -

FIGURE 8.47 -

III. BRAINSTEM AND CEREBELLUM 292 8. ORGANIZATION OF BRAINSTEM NUCLEI

16 16 smv 15 4V 15 4n DCIC 4V 4V icv VLPAG 4n 14 RC 14 E Me5 E me5 4n ECIC RC me5 Me5 13 LDTg 13 CnF LDTg LPBS 4n LC 12 DRD 12 LPB LDTgV ll Cb DRC 11 isRt 11 PDR PDR lscb lscb LDTgV DRV 10 10 DLL ll PTg DRI PTg mlf DRI mlf 9 spth 9 mtg ctg spth ctg mtg 8 8 mscb

scp 4n MnR RIs 7 7 RIs ts scp PnO VLTg MnR 6 mscb Rbd 6 Rbd PnO 5 5 mscb ipt ml 4 4 ml tth 3 xscp tth 3 xscp mcp cp 4n cp 2 2 ipt mcp MnR Pn Pn 1 1 B9 0 0 B9 tfp Rbd Pn Pn Obex +32 mm –1 –1

tfp 01234567 8 9 10 11 12 –2 Obex +33 mm FIGURE 8.49 - –3 0 1 234567 8 9 10 11 12

FIGURE 8.50 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 293

20 20 DCIC 19 19 Cb DCIC DMPAG 18 18 icv icv 17 VLPAG 17 CIC DMPAG 16 E 16 LPAG CIC E Aq ECIC Me5 15 Aq 15 VLPAG RC bic Cb 14 14 LDTg RC CnF Me5 ECIC 13 4n Sag 13 DRD DRD ll 4n ll 12 12 CnF PDR isRt DRL PBG 11 MiTg 11 DRV MiTg PBG mlf DRV isRt spth 10 DRI ctg 10 mlf Pa4 PTg spth mtg DRI mtg ctg 9 ctg 9 CIF PTg 8 8 CLi PTg RIs RIs 7 7 MnR 6 scp RRF 6 RRF DA8 scp DA8 5 5 SNL 4 4 ml CLiZ tth SNCD ipt ml 3 tth 3 SNR CLiAz Rbd 2 2 SNR xscp xscp 1 1 PBP 0 0 cp –1 –1 VTA cp csp csp IPC PIF cbu –2 cbu –2 Rbd Pn –3 –3 PN IPA –4 –4 IPL IPC –5 –5 IPI –6 –6 Pn –7 –7

–8 tfp –8 tfp –9 –9 –10 Obex +34 mm –10 Obex +35 mm –11 –11 012345678910111213 0123456789101112

FIGURE 8.51 - FIGURE 8.52 -

III. BRAINSTEM AND CEREBELLUM 294 8. ORGANIZATION OF BRAINSTEM NUCLEI

20 21 icv cic 19 DCIC 20 DMPAG 19 18 icv DLPAG DMPAG 17 18 DCIC E 16 17 LPAG CIC E Aq 15 16 LPAG VLPAG Aq CIC bic 14 15 VLPAG bic 13 RC ECIC 14 Me5 BIC DRD Me5 12 ll 13 ECIC DRD RC DRL ll 11 4n CnF spth PBG 12 DRL DRV CnF spth 10 4N Pa4 11 MiTg DRV 4n PBG mlf mtg 10 4N MiTg 9 PTg ts DRI ctg mlf 8 9 mtg isRt DRI ctg isRt 7 8 U SNL 6 7

5 RRF 6 DA8 RRF SNL 4 scp 5 DA8 tth ml CLiZ 4 3 tth PBP ml SNCD scp SNCV CLiAz 2 3 CLiZ 1 SNR 2 PBP 0 1 CLiAz SNCD xscp –1 0 SNR –2 csp –1 SNCV cbu cp csp –2 SNCD –3 PIF SNCM cp cbu rs –4 –3 IPR PIF SNCV IPR –5 –4 PN SNCM IPC –5 IPC –6 PN –6 –7 IPI IPL lfp IPI –7 IPL –8 Pn Pn –9 –8

–10 Obex +36 mm –9

–11 –10 Obex +37 mm 0123456789101112 –11

FIGURE 8.53 - 01234567891011 12

FIGURE 8.54 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 295

20 21 DMPAG icv 19 DCIC 20 Zo 18 DLPAG 19 PlGl DMPAG 17 18

16 17 DLPAG SuG LPAG 15 16 Op DpWh Aq E ECIC E 14 15 InG VLPAG Aq LPAG 14 InWh 13 RC Me5 DpG 13 VLPAG 12 dlf ECIC 12 Me5 basv 11 DRD CuF dlf RC ll bic DRD 10 Su3 spth 11 DRV Su3 PrCnF bic 9 4N 10 DRV spth isRt 8 mlf 9 3N U BIC 3N 7 ctg 8 mRt DRI U BIC DRI mtg ctg MZMG SubB 6 7 mlf CLiZ RRF mtg 5 DA8 6 RMC tth SubB MG 4 SNL 5 tth CLiZ RMC 3 ml 4 ml SNL 3n 2 scp 3 1 2 SNCD scp 0 SNCV 1 SNCD CLiAz –1 0 CLiAz –2 PBP –1 SNR PBP –3 –2 cp cp rs SNR –4 SNCV csp –3 vtgx IPDM –5 cbu –4 csp IPR PIF SNCD rs cbu –6 –5 PIF DG SNCM IPR –7 IPC –6 SNCV PN IPC CA1 –7 SNCM –8 lfp PN –9 –8 –10 –9 Obex +39 mm –10 –11 Pn Obex +38 mm –12 –11 01234567891011 12 13 14 15 012345678910111213 FIGURE 8.56 - FIGURE 8.55 -

III. BRAINSTEM AND CEREBELLUM 296 8. ORGANIZATION OF BRAINSTEM NUCLEI

21 21 20 20 scol 19 Cx Cx 19 Zo PlGl Zo 18 PlGl DMPAG 18 SuG scol 17 17 DMPAG DLPAG SuG Op 16 16 DLPAG Op InG Aq DpWh InG 15 Aq E InWh 15 InWh E Pul DpG 14 LPAG DpG 14 LPA G 13 13 DR Me5 Su3C Me5 12 Su3C DpWh 12 spth Pul Su3 spth 11 Su3 bic 11 PC3 10 PC3 BIC EW 10 mlf InCSh BIC bsc 9 I3 mRt MGD 9 3N 3N mRt ctg mtg bic 8 MGD InC 3N ctg 8 I3 7 7 MGM mtg PIL ml 6 tth MZMG 6 scp mlf MGV 5 5 PP MGV 4 scp RLi SNL 4 PP DLG ml SNL RMC SNCD 3 RMC RLi 3 2 2 ptpn 1 ocpn 1 SNCV ptpn tepn 0 scp SNCD ocpn 0 RLi SNR tepn –1 –1 PBP SND cp –2 –2 CA3 SNR cp PBP csp –3 IF –3 cbu IPDM PoDG CA1 –4 3n csp –4 DG PIF –5 PN SNCV cbu CA3 VTA –5 SNCD S IPR DG PoDG fr –6 –6 PaS IPC SNCM –7 SNCM SNCD CA1 –7 IPF SNCV –8 –8 frpn 3n –9 –9 frpn –10 Obex +40 mm –10 Obex + 41mm –11 –11 01234567891011121314151617181920 01234567891011 12 13 14 15 16 17 18 19

FIGURE 8.57 - FIGURE 8.58 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 297

21 Zo SuG 21 20 Cx 20 Cx 19 scol 19 Zo 18 18 DMPAG PlGl InWh InG SuG 17 DpWh Op 17 PlGl DMPAG Op 16 16 InG Pul DLPAG DpWh Aq InWh 15 Pul 15 DLPAG DpG E Aq LPAG 14 14 Me5 E 13 Me5 DpG 13 LPAG mRt bsc 12 Su3C 12 Su3C Dk 11 PC3 CeMe spth 11 CeMe SG SG Dk spth MGD 10 InC InCSh bsc 10 EW mRt MGD InCSh mlf MA3 InC 9 9 mlf ctg ctg mtg bic bic mtg 8 8 MGM 3N MGM PrEW PoT 7 ml PIL 7 MGV MGV RLi ml RPC PIL 6 6 scp scp ar 5 LT PP 5 RLi LT PP SNL DLG DLG 4 4 SNL LT LT 3 3 RPC SNCD 2 2 RLi PBP ptpn 1 SNR 1 PBP ptpn ocpn ecpn RMC 0 tepn 0 tepn –1 –1 SNCV –2 opt –2 SNCD cp SNCD SNR cp opt –3 –3 csp csp cbu cbu DG –4 SNCD SNCV CA3 –4 DG fr SNCV –5 VTA –5 CA3 –6 fr LV IPF PaP CA1 –6 –7 frpn –7 SNCM frpn PaP CA1 –8 –8 3n 3n –9 S –9 IPF Obex +43 mm –10 Obex + 42 mm –10 MB –11 0 1 2 3 4 5 6 7 8 9 101112131415161718192021 012345678910111213141516 17 18 19 FIGURE 8.60 - FIGURE 8.59 -

III. BRAINSTEM AND CEREBELLUM 298 8. ORGANIZATION OF BRAINSTEM NUCLEI

19 20 18 Zo 19 DMPAG SuG 17 18 Zo Op csc 16 InG 17 SuG PlGl Op 15 DpWh PlGl InWh 16 DMPAG InG Pul DLPAG InWh Pul DpG 14 DpG 15 Aq DLPAG DpWh 13 E 14 Aq 12 LPAG 13 E Me5 bsc 11 12 LPAG PLi mRt PLi MCPC 10 11 Lth p1Rt pc APT 9 Dk APT 10 InCSh InCSh spth Dk 8 InC ctg 9 InC MA3 SG mlf CeMe ctg 7 mtg 8 RPF MGD MA3 mlf mtg ml PVM MG ml ar 6 PrEW PoT 7 PrEW 5 MGV ar 6 PIL VPI scp 4 MGM 5 RLi scp LT 3 PP 4 fr RLi RPC RPC 2 SNL 3 SNL 1 2

0 SNCV ptpn 1 fr PBP ocpn ptpn –1 tepn 0 SNR ocpn PBP tepn –2 fr –1 SNCD SNR SNCV cp –3 –2 SNCD VTA –4 csp cp SNCV opt –3 opt cbu SNCV –5 VTA –4 csp cbu –6 PaP SNCV DG –5 PaP DG CA3 LV CA3 –7 –6 pm CA1 mp LV –8 IPF frpn –7 RM frpn –9 CA1 –8 Amg –10 –9 MB –11 MB BL –10 S Obex +45 mm –12 –11 –13 Obex +44 mm –14 0 1 2 3 4 5 6 7 8 9 101112131415161718192021 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 FIGURE 8.62 -

FIGURE 8.61 -

III. BRAINSTEM AND CEREBELLUM ABBREVIATIONS USED IN THE FIGURES 299

20 19 19 18 18 17

17 Pul 16 Pul 16 DMPAG 15 15 PlGl 14 Op 14 PCom 13 pc PLi 13 pc 12 PCom 12 11 APT MCPC Aq APT PLi 11 E 10 Aq E PrC p1Rt dlf 10 p1PAG 9 p1PAG 9 8 fr p1Rt RPF PVM Dk ml mtg ml 8 InC InC ctg PVM 7 eml fr ctg mlf 7 mlf 6 VPI Dk Rt 6 VPI 5 fr 5 mlf scp RLi scp mtg ZI 4 4 RPC 3 RPC STh 3 fr 2 ZI 2 1 STh 1 ptpn 0 ptpn RLi ocpn ocpn 0 tepn –1 scp SNCD tepn PBP –1 PBP VTA –2 SNR –2 SNCD SNR cp –3 SNCD cp –3 csp –4 VTAR SNCV cbu opt csp opt –4 –5 cbu –5 –6 RM –6 pm AHi AHi –7 RM –7 frpn –8 frpn –8 –9 Amg MM –9 pm Amg –10 f –10 MM ML –11 ML –11 Obex +46 mm Obex +47 mm –12 LM –12 f –13 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

FIGURE 8.63 - FIGURE 8.64 -

III. BRAINSTEM AND CEREBELLUM 300 8. ORGANIZATION OF BRAINSTEM NUCLEI

AUTONOMIC REGULATORY CENTERS up to the spinal cord. A large region of the dorsal tegmentum, mostly medial to the tract, is the solitary Dorsal Motor Nucleus of Vagus nucleus. Early studies of the solitary tract in and experimental mammals have established that the Huang and colleagues (1993a, 1993b) published tract is composed of fibers from the trigeminal and a combined cyto- and chemoarchitectonic analysis depict- facial nerves rostrally (Nageotte, 1906), the glossophar- ing the human homologs of the subnuclei of the dorsal yngeal nerve in the intermediate region and the vagus motor nucleus of vagus (10N) (Figures 8.12–8.28). The nerve caudally (Bruce, 1898; Papez, 1929; Pearson, caudal pole of the dorsal motor nucleus is found at the 1947). pyramidal decussation dorsolateral to the central canal Evidence from studies in experimental animals (caudal to Figure 8.11). At this level, it is a loose group revealed the solitary nucleus (Sol) as the initial relay of strongly AChE-positive cells. The cell bodies in 10N for , cardiac, pulmonary chemoreceptor, are prominent on a background of otherwise medium and other vagal and glossopharyngeal afferents staining. This is in contrast with the hypoglossal nucleus, (see Loewy, 1990). For example, the Sol in the rat is where the intense reaction in the obscures the known to contain neurons activated by baroreflex equally intensely reactive cell bodies. The 10N is sepa- afferents, while Sol projections to the ventrolateral rated from the hypoglossal nucleus by the intercalated part of the caudal are essential for baror- nucleus. The 10N almost reaches the ventricular epithe- eflex-induced sympathoinhibition and cardiovascular lium at the level of the area postrema (Figure 8.17). It stimulation (Guyenet et al., 1989). Visceral signals recedes from the ventricular surface accompanying the transmit via branches of the facial, glossopharyngeal, solitary nucleus, rostral to the hypoglossal nucleus. A and vagal nerves which terminate viscerotopically cell-poor and AChE-negative fringe flanks the medial across special (gustatory) and general visceral afferent aspect of 10N. A few cells can be noticed within this divisions of the solitary nucleus (Norgren, zone, a number of which are pigmented and positive for 1990). AChE and tyrosine hydroxylase (A2 cell group). Rostrally, Chemoarchitectonic analysis (Benarroch et al. 1995) 10N persists as a minor medial companion to the ventro- revealed important topographic relationships between laterally migrating solitary complex (Figures 8.13–8.28). catecholamine and nitric-oxide-synthesizing neurons, The compact rostral tip of the AChE-reactive 10N is suc- including innervation of intrinsic vessels (both ceeded by the salivatory nucleus – a scattering of AChE- tyrosine hydroxylase- and NADPH-diaphorase-reactive positive neurons that persists until nearly the level of processes innervate intrinsic blood vessels in the Sol). the exiting fascicles of the facial nerve (Figure 8.31). Such a topographic relationship may be associated Several chemoarchitectonic studies demonstrated a with regulation of autonomic reflexes, sympathetic high concentration of receptors for excitatory drive, and intrinsic control of cerebral blood (Carpentier et al., 1996a, 1996b), nicotinic acetylcholine flow in humans (Benarroch et al., 1995). Human Sol fiber (Duncan et al., 2008), serotonin (Paterson and Darnall, trajectories form three major bundles: through the inter- 2009), cannabinoid (Glass et al., 1997), D2 and D4 dopa- mediate reticular zone, across the dorsomedial reticular mine (Hyde et al., 1996), and neuropeptide FF2 formation toward the dorsa1 raphe, and a ventral one (Goncharuk and Jhamandas, 2008). In the human 10N, toward the gigantocellular reticular nucleus (Gi) cells containing adrenomedullin (Macchi et al., 2006), (Figures 8.12–8.34). The terminals were shown within met- (Covenas et al., 2004), neurokinin the Sol, dorsomotor nucleus of vagus, and reticular (Covenas et al., 2003), and bombesin (Lynn et al., 1996) formation (Ruggiero et al., 2000). Using chemoarchitec- have been found. Glial cell line-derived neurotrophic ture, To¨rk et al. (1990), then McRitchie and To¨rk (1993, factor (GDNF) immunoreactivity has been found in 1994) comprehensively delineated the human Sol. The neurons of the dorsal motor nucleus of vagus in humans lowest AChE reactivity was displayed by the ventrolat- (Del Fiacco et al., 2002). Aminopeptidase A and eral, ventral, and intermediate nuclei of Sol. Slightly angiotensin receptors have also been detected here more reactivity was displayed by the dorsal, dorsolat- (Zhuo et al., 1998; De Mota et al., 2008). Connections eral, and commissural nuclei. Intense reactivity was dis- between the dorsal motor nucleus of vagus and the soli- played by the gelatinous medial nuclei. Extremely tary nucleus have been shown in fetal human specimens, intense reactivity was displayed by the subsolitary and as in other non-human primates (Zec and Kinney, 2003). interstitial nuclei. Connections of the human solitary nucleus (Sol) have Solitary Nucleus been shown in human fetal brainstem using DiI injection to the caudal raphe at the junction of the nucleus raphe The solitary tract (sol) is a heavily myelinated fiber pallidus and the arcuate nucleus. Also connected to the bundle that extends from the level of the facial nucleus solitary are caudal hindbrain areas related to autonomic

III. BRAINSTEM AND CEREBELLUM AUTONOMIC REGULATORY CENTERS 301 and respiratory control including the dorsal motor human despite the prominent appearance of this struc- nucleus of vagus, complex/ventral ture in the rat brainstem. The human homolog of the respiratory group, rostroventrolateral reticular nucleus central subnucleus was nevertheless identified on the (RVL), caudoventrolateral reticular nucleus (CVL), and basis of strong NADPH-diaphorase reactivity by Gai the caudal hindbrain reticular formation. This connec- and Blessing (1996). tion pattern is consistent with results of other studies The commissural nucleus (SolC) lies ventromedial to on adult experimental animals (Zec and Kinney, 2003). the paracommissural nucleus and at its caudal end Ruggiero et al. (2000) identified connections between crosses the midline just dorsal to the central canal the Sol and areas of the lateral reticular formation and (Figures 8.12–8.17). The SolC is composed of very small raphe corresponding to cardiorespiratory centers in cells that tend to be mediolaterally oriented. other species. Baroreceptor reflex failure (Biaggioni The gelatinous nucleus (SolG) appears in the lateral et al., 1994), and pediatric respiratory, circulatory, and part of the solitary complex deep to the area postrema problems (Becker and Zhang, 1996) have been (Figures 8.16–8.24). It contains extremely small cells linked to the Sol in humans. that are spindle-shaped and possess that are Parathyroid receptor 2 (Bago et al., 2009), confined within the nucleus. Most cells are tyrosine nicotinic acetylcholine (Duncan et al., 2008), somato- hydroxylase positive, but are not pigmented and (Carpentier et al., 1997), and angiotensin II type have been shown to be adrenergic (PNMT positive) 1(Benarroch and Schmeichel, 1998; Zhuo et al., 1998) (Kitahama et al., 1985). The subnucleus is devoid of receptors have been found in the human Sol. Met- bombesin staining (Lynn et al., 1996). enkephalin (Covenas et al., 2004), adrenomedullin The dorsolateral nucleus (SolDL) displays fairly pale (Macchi et al., 2006), serotonin (Paterson et al., 2009), and patchy AChE reactivity (Figures 8.17–8.25). It bombesin (Lynn et al., 1996), glial cell line-derived neu- contains small and medium-sized cells arranged in rotrophic factor (GDNF) (Del Fiacco et al., 2002), and clusters, as well as large, darkly stained cells that thyrosine hydroxylase (Arango et al., 1988, Saper et al., are pigmented and tyrosine-hydroxylase-positive. The 1991) immunoreactive cell bodies, and neurokinin dorsolateral nucleus occupies the middle third of Sol immunoreactive fibers (Covenas et al., 2003) are also rostral to the level of the obex. found here. The dorsal nucleus is the rostral continuation of the The paracommissural nucleus (SolPa) is the most dorsolateral nucleus but is distinguishable by its stronger caudal representative of Sol (Figures 8.12–8.18). It and homogeneous AChE reactivity (SolD; Figures 8.23– appears at the level of the pyramidal decussation and 8.25). Cytoarchitecturally it is heterogeneous, containing ends with the advent of the gelatinous nucleus. The small and large cells. Clusters of bombesin-positive nucleus is conspicuous by its extremely rich AChE neurons were reported in the dorsal and ventrolateral reactivity. subnuclei of the human Sol (Lynn et al., 1996). Bombesin The interstitial nucleus (SolI) commences just caudal coexists with in neurons in the dorsal to the obex and persists until the accessory trigeminal subnucleus, a topographic association that may be rele- nucleus, caudal to the main mass of motor trigeminal vant to the cardiovascular effects of bombesin. nucleus; thus, it is the longest and the most rostral repre- The medial nucleus (SolM) (Figures 8.14–8.28)isthe sentative of Sol (Figures 8.18–8.34). It is closely associ- strongly AChE-reactive region located between the ated with the solitary tract, at times enveloping it and dorsal, dorsolateral, ventral, and gelatinous nuclei. It at times being enveloped by it. The SolI expands at its is composed mainly of very small cells, although rostral pole. It is at these levels in the monkey and a few larger pigmented cells are also visible. The human that the nucleus has a gustatory function. medial nucleus replaces the commissural nucleus Possible gustatory function more posteriorly is sug- rostrally (Figure 8.14) and becomes a rectilinear shape gested by the contributions of the ninth and tenth as it occupies the full dorsolateral extent of Sol nerves, but has not yet been confirmed. Pritchard, in bordering 10N medially (Figures 8.19–8.28). Further Chapter 33, provides a comprehensive review of the rostrally, it separates 10N from the interstitial nucleus gustatory role of SolI. of Sol. The medial nucleus disappears with the loss Paxinos and Huang (1995) had recognized a nucleus of 10N (Figure 8.29). A chemoarchitectonic study they called the subsolitary at the rostroventral border reported strong bombesin fiber/terminal staining in of the interstitial solitary nucleus, by its extremely strong the medial subnucleus of Sol over its full rostrocaudal AChE reactivity. Paxinos and Watson (2007), in the rat, extent in both rat and human (Lynn et al., 1996). have renamed this area the trigeminosolitary nucleus Another study found the dopamine D2 and D4 recep- because it is the annectant area. tors to be almost exclusively concentrated in the inter- Paxinos and Huang (1995) using AChE staining failed mediate and medial subnuclei of Sol (Hyde et al., to identify the central subnucleus of the Sol in the 1996).

III. BRAINSTEM AND CEREBELLUM 302 8. ORGANIZATION OF BRAINSTEM NUCLEI

The parasolitary nucleus (PSol) is a conspicuous, The medial parabrachial (MPB) nucleus begins more AChE-negative, banana-shaped nucleus (with a lateral caudally than the lateral parabrachial and is well dis- concavity) featuring small, densely packed cells at the played at the compact locus coeruleus pars alpha (Figures lateral border of Sol. It commences at about the level 8.17–8.48). The intensity of AChE staining varies between of the obex caudally and persists until the rostral third cell groups, but sometimes also between species; thus, of the hypoglossal nucleus (Figures 8.18–8.22). unlike the rat, the human MPB is strongly AchE-positive, Cheng et al. (2006) investigated the prenatal develop- especially in its juxtabrachial portion. It is limited rostro- ment of the cyto- and chemoarchitecture of the human ventrally by the central tegmental tract before the rostral Sol from 9 to 35 weeks, using Nissl staining and end of the lateral parabrachial nucleus. The medial part calbindin, calretinin, tyrosine hydroxylase, and GAP- of MPB directly overlies the ventromedial aspect of the 43 immunohistochemistry. They observed that the Sol superior cerebellar peduncle and is strongly reactive for started to show different subnuclei as early as 13 weeks AChE. The external part of MPB is distinguished by lower and approached cytoarchitectural maturation from 21 AChE reactivity than its medial part. to 25 weeks. Calbindin-immunoreactive neurons first The lateral parabrachial nucleus (LPB) attains its full appeared in the medial gastrointestinal area and tyro- extent at the caudal pole of the dorsal tegmental nucleus sine-hydroxylase-immunoreactive neurons in the (Figures 8.39–8.49). The AChE-positive central part of medial subdivisions of the Sol, starting from week 13. LPB succeeds the pedunculotegmental nucleus caudally, Strong GAP-43 immunoreactivity was also present which is distinguished by stronger AChE reactivity. The in the Sol at week 13, while a significant decline was dorsal part of LPB is, in contrast, poorly stained for observed at week 21. AChE. The external part of LPB is AchE-positive. A quantitative autoradiographic study of human fetuses Parabrachial Nuclei revealed a sharp decrease in the density of somatostatin- binding sites on late stages of gestation (Carpentier et al., The parabrachial nuclei (PB) are pivotal structures in 1997). autonomic control because they perform as an interface Gioia et al. (2000) investigated the cytoarchitecture of between the medullary reflex control mechanisms and adult human PB using Nissl and Golgi stains. They the behavior and integrative regulation of observed that the PB is composed of small to central autonomic systems. While 13 distinct subnuclei medium-sized, round, oval, elongated or polygonal- have been identified in the rat PB (Fulwiler and Saper, shaped neurons. The cells were larger on the medial 1984; Herbert et al., 1990), only five have been discov- PB when compared to the lateral part. Fusiform neurons ered thus far in primates (Paxinos et al., 2009). Relative had two primary dendrites with occasional small to the rat, the human PB are cell poor and it is not spines. Primary dendrites of multipolar neurons had obvious that there are human homologs to the numerous scant secondary dendritic ramifications. In the medial subdivisions described in the rat. Fortunately for PB, the multipolar and fusiform neurons showed the study of homologies, most of the PB subnuclei are thinner primary dendrites and wider secondary chemically specified and project via somewhat distinct dendritic arborizations when compared to the lateral chemically coded lines to their terminations in the hypo- parabrachial nucleus. Another study in humans and medial part of the of (Lavezzi et al., 2004) showed that the medial PB con- the thalamus (see Chapter 19). The chemically coded tained oval and polygonal neurons were usually larger afferent projections to the PB are also instructive in than the lateral PB neurons, with darker and more establishing subnuclei or homologies and their projec- evident cytoplasms. tions in the human. For example, consider the known Calcitonin -related (a neuromodulator in catecholaminergic, cholecystokinin-, galanin-, and corti- efferent projections from PB to the thalamus and amyg- cotropin-releasing hormone immunoreactive projec- dala in rats) was employed as a marker for ascending tions from Sol to the PB in the rat (Herbert and Saper, visceral sensory pathways in the human brain (de 1990; Phillips et al., 2001). Somatostatin receptors are Lacalle and Saper, 2000). As well as in establishing also found in PB (Carpentier et al., 1996a, 1996b). affiliations of the human PB, chemoarchitecture of The central part of the human lateral PB contains MPB and LPB may be of value in pathological investiga- AChE reactivity, while the dorsal part of the lateral PB tion. Carpentier et al. (1998) found that the density of is poorly stained for the enzyme. The external part of somatostatin-binding sites was significantly elevated in the lateral PB is also AchE-positive and probably corre- MPB and LPB in the sudden infant syndrome. sponds to the pigmented nucleus mentioned by Ohm Calcitonin gene-related peptide (de Lacalle and and Braak (1987). The human homolog of the most Saper, 2000), glial cell line-derived neurotrophic factor medial part of the medial PB has also been identified (GDNF) (Del Fiacco et al., 2002, Quartu et al., 2007), by AChE staining. neurokinin (Covenas et al., 2003) and thyrosine-

III. BRAINSTEM AND CEREBELLUM AUTONOMIC REGULATORY CENTERS 303 hydroxylase (Ikemoto et al., 1998) immunoreactive LPB, tapering off as a row of cells on the dorsal part of neurons, and parathyroid hormone (Bago et al., 2009), PB. At this most rostral level, only a few pigmented cells angiotensin II type 1 (Benarroch et al., 1998; Zhuo are seen, but the characteristic AChE reactivity is present. et al., 1998) and somatostatin (Carpentier et al., 1997) The cells of SPP are polygonal with no specific orienta- receptors have been observed in the human PB. tion. Ohm and Braak (1987) observed neurofibrillary In the human, Ko¨lliker-Fuse nucleus (KF) extends tangles on this nucleus in brains from Alzheimer disease from the caudal pole of the parabrachial nuclei in the patients. Incidentally, considering their pivotal role rostral hindbrain to the lower portion of the mesenceph- within central autonomic regulatory systems, the nuclei alon. Lavezzi et al. (2004) examined the human KF in of the caudal hindbrain parabrachial region (MPB, LPB, newborns and infants, and described the KF as a group SPP) together with the intermediate zone of the reticular of large neurons, ventrally located to the lateral parabra- formation (IRt) are to be targets of the Alzheimer chial nucleus between the medial limit of the superior disease-related pathology (Rub et al., 2001). In another cerebellar peduncle and the medial lemniscus. The KF study, Ohm and Braak (1988) described three basic neurons were noticeably larger than those of the para- neuronal types in SPP: neuromelanin-containing type I brachial nuclei. On the basis of the neuronal arrange- nerve cells, type II cells with lipofuscin deposits, and ment, Lavezzi et al. (2004) define two KF subnuclei: type III neurons devoid of any pigmentation. The SPP the subnucleus compactus which consists of a cluster is not the homolog of the KF or of any other known of a few neurons and has an indistinct outline, and the nucleus in experimental animals. subnucleus dissipatus adjacent to the subnucleus compactus. Periaqueductal Gray In the rat, KF was proposed to harbor the most lateral cluster of the A7 noradrenergic group (Paxinos and The periaqueductal gray (PAG) is an important central Watson, 1998). We note, however, that KF does not relay in cardiovascular and other autonomic control and form a well-circumscribed group in the rat, whereas in modulation of . There is also substantial evidence for the cat, KF has been placed everywhere in the region human homologies to the PAG subdivisions established between the superior cerebellar peduncle, the lateral in rat and cat (Beitz, 1985; Bandler et al., 1991; see also lemniscus, and the motor trigeminal (see discussion by Chapter 10). Thus, Paxinos and Huang (1995) identified Berman, 1968). Paxinos and Huang (1995) depicted the dorsomedial, dorsolateral, lateral, and ventrolateral location of the nucleus in the human brainstem (Figures PAG columns in the human (Figures 8.51–8.64). Another 8.40–8.45). chemoarchitectonic investigation based on NADPH- Fix (1980) identified a melanin-containing nucleus diaphorase reactivity (Carrive and Paxinos, 1994) recog- associated with the superior cerebellar peduncle. He nized the supraoculomotor cap in the human PAG. The labeled the nucleus “X”, using inverted commas presum- posterior part of this cap was subsequently distinguished ably to indicate that he did not wish this to be retained as by AChE staining (Paxinos and Huang, 1995). Paxinos its name. Ohm and Braak (1987) identified the same and Huang (1995) also outlined the human pleoglial nucleus and called it the subpeduncular nucleus. This PAG – a median structure above the rostral levels of the term can be easily confused with the subpeduncular aqueduct. Like the parabrachial nucleus, the PAG forms tegmental nucleus (Paxinos and Watson, 1998); for this an interface between the forebrain emotional system , Paxinos and Huang (1995) used the term subpe- and autonomic centers. It receives afferents from the duncular pigmented nucleus, as did Ohm and Braak in hypothalamus and and in turn projects to the the title of their abstract. The subpeduncular pigmented intermediate reticular zone. Carrive et al. (1989) showed nucleus (SPP) is unmistakably AchE-positive in neuropil that the PAG autonomic control is compartmentally orga- and cell bodies. It has relatively large, tightly clustered, nized into PAG columns and coupled to defensive neuromelanin-containing cells presenting a globular behavior in the rat. Paxinos and Huang (1995) showed profile in coronal section. Because SPP is attached to a columnar arrangement for the human PAG, which is the ventrolateral edge of the superior cerebellar discussed in detail by Carrive (in Chapter 10). peduncle, reaching the lateral lemniscus at the surface, A somatosensory homonculus has also been sug- it has cell-poor and fibrous regions surrounding it. gested in the human PAG by Bittar et al. (2005), with Caudally, it commences before the lateral parabrachial the lower limbs represented rostrally and the head nucleus as a group of mainly non-pigmented cells ventral caudally, and the trunk and upper limbs occupying an to the superior cerebellar peduncle. More rostrally, it is intermediate position. This somatosensory representa- very favorably displayed and appears as a globular tion is contralateral, except for the forehead and . nucleus at the ventrolateral edge of the superior cere- In the human PAG, receptors for parathyroid bellar peduncle with the majority of its cells pigmented. hormone 2 (Bago et al., 2009), GABA-B (Serrats et al., Further rostrally, it drifts dorsally and intrudes into 2003) and angiotensin II type 1 (Benarroch and

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Schmeichel, 1998) have been found. There are also neu- the polarity of cell bodies and their major dendrites. rokinin (Covenas et al., 2003), bombesin (Lynn et al., These cells are oriented along the dorsomedial to ventro- 1996) thyrosine hydroxylase (Counhian et al., 1998), lateral axis, mirroring the shape of the zone in coronal met-enkephalin (Covenas et al., 2004) and thyrosine sections. This orientation predilection distinguishes the hydroxylase (Benarroch et al., 2009) immunoreactive IRt from the adjacent gigantocellular and parvicellular cell bodies, and substance P, pituitary adenylate- reticular nuclei that contain neurons with various cyclase-activating peptide (PACAP) and vasoactive orientations. intestinal polypeptide (VIP) (Tajti et al., 2001) containing fibers. Position The nucleus of Darkschewitch (Dk) is found in the Caudally, the IRt separates the dorsal from the periaqueductal gray, dorsomedial to the interstitial ventral reticular nuclei; rostrally, the IRt separates the nucleus of the medial longitudinal fasciculus at a level gigantocellular from the parvicellular reticular nuclei posterior to the ascending fasciculus retroflexus. It is (Figures 8.5–8.33). The zone commences at the pyra- non-distinct in AChE preparations. midal decussation and extends to the facial nucleus. It is a convex arc with the convexity facing laterally in RETICULAR FORMATION the rat but medially in the human (probably due to the enormity of the human inferior olive). Dorsally, outlying tyrosine-hydroxylase-positive cells of this The keystone to the organizational plan of the retic- zone are found in the cell-poor region that caps the ular formation in rhombomeres 4–11 offered in this medial pole of the dorsal motor nucleus of vagus. chapter is the intermediate reticular zone (IRt). Laterally, it has a variable extent. At caudal levels, IRt reaches the lateral surface of the caudal hindbrain Intermediate Reticular Zone dorsal to the lateral reticular nucleus (LRt) (Figures 8.14–8.17). Somewhat rostrally, IRt bisects the LRt in Historical Considerations its surge to the lateral surface (Figures 8.23, 8.24). In 1986 the intermediate reticular nucleus of the rat Further rostrally, it forms a slab dorsal to the lateral was recognized as the zone between the gigantocellu- paragigantocellular nucleus and together they reach lar and parvicellular reticular nuclei which contains the lateral surface (Figure 8.30). Caudally, it harbors large, medium, and small cells and is slightly more the retroambiguus, ambiguus, and Al noradrenaline reactive for AChE than its neighbors (Paxinos and (norepinephrine) cell groups. Rostrally, it harbors the Watson, 1998). Presumably, this zone brackets the ambiguus nucleus as well as the C1 adrenaline line separating the alar and basal plate derivatives in (epinephrine) group. development. The line extends radially from the sulcus limitans in the floor of the fourth ventricle to the Catecholamine Cells periphery of the brainstem where the vagal and glos- Catecholamine cells are found throughout the IRt sopharyngeal rootlets emerge. Due to its cytoarchitec- but are more prominent in the part ventrolateral to the ture and position, the zone was named the ambiguus nucleus (Al and C1). These regions of the intermediate reticular nucleus. Allien et al. (1988) IRt have been called the caudoventrolateral (CVL) and found a distinct punctuated distribution of angiotensin rostroventrolateral (RVL) reticular nuclei of the medulla II receptors over cell bodies in what they proposed to (Arango et al., 1988). This cell group is thought to be be the human homolog of the rat intermediate reticular involved in control of sympathetic cardiovascular nucleus (see also Allien et al., 1991). Halliday outflow, cardiorespiratory interactions, and reflex and colleagues (1988b, 1988c), and later Huang and control of release. For example, a pathology colleagues (1992), showed tyrosine hydroxylase, and study showed depletion of catecholaminergic tyrosine- neuropeptide Y (NPY) cell bodies and fibers in what in hydroxylase-positive neurons in patients with multiple fact is the intermediate reticular nucleus. system atrophy with autonomic failure (Benarroch Based on the evidence for the existence of the inter- et al., 1998). The full extent of IRt can be clearly seen mediate reticular zone in humans and, following in Figure 4 of Arango et al. (1988), which depicts tyro- mappings of tyrosine hydroxylase, serotonin, NPY, sine hydroxylase immunoreactivity in the caudal hind- and substance P in this area, Paxinos and Huang brain. This observation was later successfully used by (1995) proposed an extension of IRt boundaries. Given Huang et al. (1992) for delimiting IRt on the basis of the heterogeneity of this area (see below), they changed the distribution of the tyrosine-hydroxylase-immunore- its name from “intermediate reticular nucleus” to “inter- active cells and fibers. The distribution of AChE-positive mediate reticular zone” (IRt). The hallmark of the cells in the IRt resembles the distribution of the catechol- cytoarchitecture of the intermediate reticular zone is amine-containing cells. The most distinct AchE-positive

III. BRAINSTEM AND CEREBELLUM RETICULAR FORMATION 305 neuropil is associated with RVL at levels where the homogeneous. Rostrally, IRt displays a band of ambiguus nucleus is most prominent. This AChE reac- substance-P-positive fibers and cells near its border tivity in the IRt (RVL) is associated with cell bodies with the parvicellular reticular nucleus. The ambiguus and fibers and it nearly reaches the lateral surface of nucleus is the most substance-P-poor region of the IRt. the brain. Caudally, the IRt contains a few substance-P-positive cell bodies that are larger than the substance-P-positive Neuropeptide Y cells in the parvicellular reticular nucleus. All NPY-reactive neurons are found throughout the ros- substance P cells in the IRt also contain adrenaline trocaudal extent of the ventrolateral IRt, particularly at (epinephrine) or noradrenaline (norepinephrine). midolivary levels. Expression of NPY mRNA has also However, most (about 95%) of the catecholamine cells been reported in IRt (Pau et al., 1998). Benarroch and do not contain substance P (Halliday et al., 1988a). Ni Smithson (1997) described tyrosine hydroxylase and and Miller Jonakait (1988) have shown that substance NADPH-diaphorase distribution in the IRt. The distri- P fibers excellently delineate IRt in the developing bution of NPY immunoreactivity overlaps tyrosine mouse. hydroxylase but not NADPH-diaphorase reactivity (Benarroch and Smithson, 1997), suggesting a possi- Salmon Calcitonin-Binding Sites bility of further subdivision of human ventrolateral The IRt can also be delineated by the salmon calci- IRt. tonin-binding sites (Sexton et al., 1994). It is important to mention, though, that these sites invade some regions Serotonin of the parvicellular reticular nucleus and the gigantocel- Caudally, the lateral part of the IRt contains some lular nucleus. IRt neurons have also been shown to serotonin cells intermixed with the catecholamine cells, contain nicotinic acetylcholine receptors in humans though differentially concentrated. Many of these cells, (Duncan et al., 2008). particularly serotonin cells, are very close to the surface of the caudal hindbrain. The more rostral regions of IRt Connections contain only occasional serotonin cells. At rostral levels, There is evidence that cells contained in the IRt have most serotonin cells are distributed in the lateral paragi- both ascending and descending connections. For gantocellular nucleus, immediately medioventral to IRt example, following small HRP injections into the para- (Figure 8.30). brachial region in cats, King (1980) found separate sheets Other studies have also shown serotonin cells in the or layers of retrogradely labeled cells in “lateral lateral (Paterson and Darnall, 2009) and dorsal (Fonseca tegmental field” (Berman, 1968) that ran parallel to the et al., 2001) parts of the IRt in humans. At times, some long axis of the lower brainstem and radially with chemically specified cell groups do not respect classical respect to the ventricle. The more medial gamma and nuclear boundaries and no adjustment of boundaries delta layers of labeled cells of King’s (1980) description can be made that can accommodate the new elements appear to occupy the medial region of the lateral without violating other delineation criteria. However, tegmental fields (or parvicellular reticular formation the IRt has consistently appeared as an entity in the (PCRt in our terminology)) that we have now incorpo- work of a number of investigators who have used retro- rated into the IRt. Similarly, HRP injection into the grade or anterograde labels or different chemically caudal vagosolitary complex produced a comparable specific stains. Having obtained an “after image” from sheet of labeled cells extending the length of the cat’s the pattern of distribution of chemically specified medulla in what Mehler (1983) also then called the elements, it is possible to detect, in Nissl-stained medial part of the PCRt but which we now consider sections, fusiform cell bodies that are oriented in the part of the IRt zone. Interestingly, anterograde tracer direction of the axis that joins the dorsal motor injection experiments involving IRt in the rat produce nucleus/solitary complex dorsomedially with the Al/ confirmatory evidence of ascending projections to the Cl cell groups ventrolaterally. The existence in the IRt parabrachial region and descending projections to the of “independent” nuclei, that do not share IRt proper- solitary nucleus and the phrenic motoneuron pools at ties, prompted us to reclassify this region from a nucleus C4 (Yamada et al., 1988). to a zone. In the monkey, injections of HRP into the cervical vagus nerve result in heavy retrograde labeling of Substance P neurons in the ipsilateral dorsal motor nucleus of Substance P is differentially distributed in the vagus and in the ambiguus nucleus. “Additionally, caudal hindbrain reticular nuclei. IRt displays more a few neurons are labeled in the intermediate zone substance-P-positive fibers than adjacent nuclei. The between these two nuclei” (Gwyn et al., 1985), i.e., in distribution of substance P fibers in IRt is non- the IRt.

III. BRAINSTEM AND CEREBELLUM 306 8. ORGANIZATION OF BRAINSTEM NUCLEI

Retroambiguus and Ambiguus Nuclei animals, and likewise we have placed it in the human by position. The RAmb commences below the pyramidal decussa- tion as a scatter of AChE-positive cells embedded in the Ventral, Medial, and Dorsal Reticular Nuclei part of the IRt that is separated from the rest by the decussating corticospinal fibers. It succeeded rostrally Considering that the existence of the IRt is accepted, (Figure 8.10) by the ambiguus nucleus loose part the remainder of the reticular formation of the caudal (AmbL) which we define according to its position rela- hindbrain can be subdivided in a scheme that is in tive to the rat, where it has been identified properly. In harmony with the distribution of neuroactive turn, the loose part is succeeded by the ambiguus compounds in this area. nucleus, semicompact part (AmbSc). After all parts of The area dorsal and ventral to the IRt (previously the inferior olive have fully formed, AmbSc gives way known as medullary reticular nucleus) features two to ambiguus nucleus compact part (AmbC). At the point distinct nuclei. We call these the medullary reticular of hand-over, there is a sudden dorsomedial rise in the nucleus, ventral part (MdV) and the medullary ambiguus column (Figuer 8.24). RAmb is characterized reticular nucleus, dorsal part (MdD), in consistency by diffuse spindle-shaped cells. Amb, by contrast, has with the same areas in experimental animals. These large multipolar neurons that stain densely for AChE were previously known as MRt (medial reticular and display large Nissl granules. At area postrema nucleus of the medulla) and VRt (VRt ventral reticular levels the Amb is represented by only a few cells nucleus; Paxinos and Huang, 1995). The area ventrome- (Figures 8.17–8.19). At the level of the caudal pole of dial to IRt is the MdV and area dorsolateral to IRt is the dorsal accessory olive, it expands ventrolaterally the MdD. Both MdV and MdD hand over to Gi and to conform to the arcuate shape of the IRt (Figures PCRt at the rostral pole of the linear nucleus 8.20, 8.21). It becomes a round cluster near the level (Figure 8.21). of the rostral pole of the hypoglossal nucleus and The caudal pole of the IRt is found at a ventrolateral attains maximal size near the level of the roots of the position below the retroambiguus nucleus (RAmb). glossopharyngeal nerve (Figure 8.22). At this level, Rostrally, it is displaced medially and dorsally by the the AChE reactivity associated with the Amb engulfs advancing linear nucleus (Li), which in turn is displaced the surrounding cell-poor zone. medially and dorsally by the lateral paragigantocellular Unlike other regions of IRt, RAmb and Amb do nucleus (LPGi) (Figure 8.21). All these nuclei border the not possess catecholamine or NPY cells and are not inferior olive principal nucleus (IOPr) ventrally and the invaded by catecholamine- or NPY-containing processes. IRt dorsally. On the other hand, the human adult Amb contains The MdD contains large catecholaminergic neurons serotonin-immunoreactive fibers (Halliday et al., 1990) distinguishable by strong tyrosine hydroxylase immu- and the human fetal Amb contains high concentrations noreactivity and contains smaller cells and fewer of somatostatin receptors (Carpentier et al., 1996a, substance P fibers than medullary reticular nucleus, 1996b). In addition, monoamine oxidase A, substance P, ventral part (MdV) (Figures 8.4–8.20). and receptors for angiotensin II are scarcest in the Studies in experimental animals have shown that RAmb and Amb regions of the IRt (Paxinos et al., the MdD neurons are activated only or mainly by 1990). Neurokinin-immunoreactive fibers have also noxious stimulation (Villanueva et al., 1988) and are been shown in Amb of humans (Covenas et al., 2003). immunoreactive for several amino acids, , and The mode of integration of the ambiguus column non-opioid and monoamines including with the remainder of IRt is still unclear. A case descrip- glutamate, GABA, acetylcholine, substance P, catechol- tion provided insight into the role of Amb, Sol, and amines, and serotonin (Lima et al., 2002). It is thought neighboring caudal hindbrain reticular formation as that MdD serves as a primary pro-nociceptive center well as the vagal dorsal motor nucleus in central control in the pain control system that integrates multiple of swallowing. Thus, lateral medullary syndrome pre- excitatory and inhibitory actions for nociceptive pro- sented with numerous symptoms, including dysphagia, cessing (Villanueva et al., 2000; Lima and Almeida, is associated with lesions in the upper caudal hindbrain 2002). (Martino et al., 2001). The rostroventral respiratory group (RVRG) has Mesencephalic Reticular Formation been placed under the semicompact ambiguus (AmbSC) in the rat. We have likewise placed it in the Paxinos and Huang (1995) formerly identified an human by position without other evidence. Pre-Bot- AchE-positive area in the human adjacent to ctg zinger (PrBo) and Botzinger (Bo) complexes have been which was circumscribed but not labeled (Figures placed under the compact ambiguus in experimental 8.62, 8.63). We now identify this area as a homolog of

III. BRAINSTEM AND CEREBELLUM RETICULAR FORMATION 307 the retroparafascicular nucleus (RPF) in the mouse, rat, The parvicellular part of LRt (LRtPC) betrays its pres- and monkey. Immediately caudal to this area, we see ence in the rat by the extremely dense AChE reactivity. a condensation of cells that we think is a human In the human, AChE reactivity is found in islets near homolog of the mouse central mesencephalic nucleus the surface of the lateral caudal hindbrain immediately (CeMe) identified by Franklin and Paxinos (2008).This external to LRt (Figure 8.21). These small compact cells is a calbindin-positive cell group and this name was poorly stained for Nissl and associated with this reac- given by topology. tivity belong to the homolog of LRtPC. In humans its size is clearly attenuated in comparison with that in the rat. Human LRt contains high densities of neuroki- Lateral Reticular Nucleus nin-immunoreactive fibers (Covenas et al., 2003). For further details on LRt, see Walberg (1952). The lateral reticular nucleus (LRt) consists of the lateral reticular nucleus proper, the subtrigeminal divi- Gigantocellular, Lateral Paragigantocellular, sion, the linear division, and the parvicellular division. Gigantocellular Ventral Part, Gigantocellular The LRt proper has AChE-positive neurons in a some- Alpha Part, and Dorsal Paragigantocellular, what dense neuropil that is perforated by negative fibers and Parvicellular Reticular Nuclei with longitudinal orientation. It commences caudally at the rostral part of the pyramidal decussation (caudal to The gigantocellular reticular nucleus (Gi) appears Figure 8.12). According to Paxinos et al. (1990), the name together with Roller’s nucleus (Figure 8.21). It extends “lateral reticular nucleus” is retained only for this part of to the level of the exiting facial nerve, where it is suc- the nucleus (without qualifiers such as “proper” or ceeded by the caudal part of the pontine reticular nucleus “principal”). (PnC) (Figure 8.32). A study of the cytoarchitectonic The subtrigeminal LRt (LRtS5) features large cells, development of the human Gi suggested that immature well stained for AChE, in a dense AChE background. Gi neurons appear by 16 weeks of gestation after migra- It commences caudal to the principal inferior olive tion and that the subsequent differentiation and matura- (Figure 8.12). At its rostral pole it becomes fractionated tion progresses gradually and monotonously during the and discontinuous (Figure 8.27). The LRtS5 also latter half of gestation (Yamaguchi et al., 1994). contains tyrosine-hydroxylase-positive neurons. The The present description of the lateral paragigantocel- LRtS5 together with MdV and MdD is thought to lular nucleus (LPGi) is based on the distribution of sero- play a role in autonomic respiratory centers in the tonin cells. LPGi first appears lateral to the rostral pole of caudal hindbrain. In support of this view, Ono et al. the linear nucleus (Figures 8.21, 8.22). LPGi remains at (1998) reported severe loss of catecholaminergic a lateral position and always ventromedial to the IRt. (tyrosine-hydroxylase-positive) neurons in LRtS5, When the dorsal accessory olive disappears, the LPGi MdD, and MdV in patients with myotonic dystrophy expands medially, where it persists until the rostral who suffered alveolar hypoventilation and respiratory pole of the principal inferior olive (Figures 8.27, 8.28). insufficiency. Along its entire length, LM features many fusiform sero- The LRt extends medially over the caudal pole of the tonin-containing neurons. Beyond the caudal pole of inferior olive. This linear part becomes separated from LM, serotonin cells remain in the region but do not pene- the main LRt at the caudal pole of the dorsal accessory trate the linear reticular nucleus; rather, they shift olive. Paxinos and Huang (1995) named this epiolivary dorsally into the IRt and mingle with the tyrosine- nucleus, but we now find that it is the homolog of the hydroxylase-positive cells of this zone. The spread of linear nucleus in rodents. Further rostrally, it shifts medi- the LPGi as shown by Nissl staining matches that of ally as a compact rectangular group (Figures 8.12–8.27). the serotonin-positive cell bodies. More than 150 sero- Paxinos and colleagues (1990) noticed in the baboon tonin-positive cells can be seen on each side of a 50-mm a nucleus in a position similar to the linear LRt that section of the caudal hindbrain. The serotonin-positive displays large retrogradely filled cells following thoracic cells are larger in the LPGi (27 Æ 4 mm) than in the caudal HRP injections. This spinally projecting nucleus in the part of the intermediate reticular zone (19 Æ 4 mm) baboon cannot be assigned to LRt because it projects to (Halliday et al., 1988a). the spinal cord rather than the cerebellum. Therefore, Substance P is found in many of the serotonin- the linear nucleus may not belong to LRt complex, containing cells in the LPGi (Halliday et al., 1988b). although the two nuclei are nearly identical morpholog- Zec and Kinney (2001) examined proximal projections ically (Paxinos et al., 1990). The similarity of the linear of LPGi using a bidirectional lipophilic fluorescent nucleus to LRt was also recognized by Braak (1971). tracer, 1,1’-dioctadecyl-3,3.3’,3’-tetramethylindocarbo- We are now convinced that the epiolivary nucleus is cyanine perchlorate (DiI), in postmortem human fetuses homologous with linear nucleus (Fu et al., 2009). and reported diffusion of DiI to the arcuate nucleus (Ar),

III. BRAINSTEM AND CEREBELLUM 308 8. ORGANIZATION OF BRAINSTEM NUCLEI nudeus raphe obscurus, hilus of the inferior olive, bilat- TEGMENTAL NUCLEI eral Gi, and the intermediate reticular zone (IRt), vestib- ular and cochlear nuclei, cells and fibers at the floor of Ventral Tegmental Nucleus the fourth ventricle, medial lemniscus, lateral lemniscus, inferior cerebellar peduncle and cerebellar , In 1884, von Gudden observed that in the rabbit the central tegmental tract, and capsule of the red nucleus. majority of the fibers of the mammillotegmental tract The LPGi contains the adrenergic cell group C1 and terminated in a distinct nucleus of the pontine the noradrenergic A1, A2, A4, and A5 cell groups. tegmentum that he named after himself, “das Gudden- Studies on experimental animals have shown that acti- sche .” This nucleus is now known as the vation of serotonergic cells in the LPGi triggers solitary ventral tegmental nucleus (von Gudden, 1884) (VTg) nucleus-mediated cardiac baroreflex inhibition elicited and is a densely packed, conspicuous nucleus in all by noxious stimuli (Gau et al., 2009). species studied except the human. The Gi, ventral part (GiV) is an AChE-poor area On the basis of chemo- and cytoarchitecture, Paxinos above the dorsal accessory olive. It borders the LPGi et al. (1990) and, soon after, Huang et al. (1992) delin- and IRt laterally and the Gi dorsally. Unlike the rat, eated VTg in humans as the large, AChE-reactive cat, and monkey, the human GiV does not have giant nucleus that succeeds rostrally the abducens nucleus, cells. It is succeeded rostrally by the gigantocellular after allowing the root of the seventh nerve to interpose alpha-part (GiA). itself between the two nuclei. This area is not a rostral The GiA forms a cap over the raphe magnus (Figures extension of the abducens nucleus because both nuclei 8.30–8.32). It has small, medium, and large cells, many of taper prior to reaching either side of the root of the which are oriented mediolaterally. It is bordered later- seventh nerve. The VTg, according to them, is ally by the central tegmental tract as the tract approaches embedded in the lateral aspects of the medial longitu- the inferior olive. It is characterized by medium AChE dinal fasciculus (mlf), extending both ventrally into reactivity and has AChE-positive cell bodies. In addi- the tegmentum and dorsally into the central gray. tion, serotonin-positive cells invade the ventral and According to them, the VTg is succeeded rostrally by lateral part of the GiA (see Chapter 32). The dorsal para- the alar interstitial nucleus. gigantocellular nucleus (DPGi) is favorably seen in In the first edition of the atlas (Paxinos and Huang, Figure 8.32 as an AChE-poor region. DPGi is located in 1995), there were errors in VTg and AlI. We are con- the dorsomedial part of the rhombomeric tegmentum, cerned that the location where Paxinos et al. (1990) lateral to the medial longitudinal fasciculus, ventral to placed it is in rhombomeres further caudally than it is the prepositus hypoglossal nucleus, and dorsal to the present in experimental animals. Therefore, in the gigantocellular reticular nucleus (Figures 8.23–8.32). present atlas, we do not recognize a VTg and now call DPGi contains loosely and irregularly arranged nerve this AchE-positive cell group an extension of the reticu- cells, including round, ovoid, triangular small neurons, lotegmental nucleus the lateral part (RtTgL). We think slender, triangular or multipolar medium-sized, and that VTg should end ventrolateral to PDTg, and AlI is occasionally large neurons (Bu¨ ttner-Ennever and Horn, now changed to VTg. 2004; Ru¨ b et al., 2008). Dorsal Tegmental Nucleus Descending projections from the GiV pars alpha and LPGi to the spinal cord have been shown in rats, to the Caudally, the dorsal tegmental nucleus (DTg) intermediolateral and the sacral parasympathetic commences at the level of the rostral pole of the reticular nucleus, as well as to regions of the intermediate gray, tegmental nucleus (Figure 8.38). It was first identified by and to laminae 7–9 and 10 throughout the length of von Gudden (1889, cited by Berman, 1968). Chemo- and the spinal cord. These diffuse projections suggest that cytoarchitectonic study of the nucleus in the human Gi is involved in the direct, descending control of (Huang et al., 1992) delineated DTg as a circumscribed, a variety of spinal activities (Hermann et al., 2003). Elec- compact, small-celled nucleus conspicuous by its rela- trophysiological and physiological studies in rats have tively poor AChE reactivity, which contrasts sharply also shown that the GiV pars alpha and LPGi provide with the dense laterodorsal tegmental nucleus (Figures descending control of pelvic floor organs, specifically 8.43–8.48). It extends to the caudal pole of the peduncu- by inhibition of sexual reflexes (Hubscher and Johnson, lotegmental nucleus (PTg). The DTg was erroneously 1996; Johnson and Hubscher, 1998). considered to be part of the supratrochlear nucleus The juxtaolivary nucleus (JxO) is an AchE-positive (dorsal raphe in current nomenclature) by Olszewski cell group dorsal to the rostral inferior olive, first identi- and Baxter (1954). The DTg is completely devoid of sero- fied in the rat (Paxinos and Watson, 2007). In the human, tonin cells, and this supports the original classification of JxO lies between the lateral extension of LPGi and the von Gudden (1889) that distinguished it from the raphe olive (Figures 8.25–8.28). nuclei.

III. BRAINSTEM AND CEREBELLUM LOCUS COERULEUS 309

Glial cell line-derived neurotrophic factor (GDNF) rodent is, in fact, the homologue of the PTg pars dissipata of (Del Fiacco et al., 2002, Quartu et al., 2007)and primates. We have studied AChE sections of human, monkey and rat brains and have confirmed that the PTg in all three corticotropin-releasing hormone (Austin et al., 1997) species is strongly AchE positive in cells and neuropil. immunorective neurons have been observed in the Furthermore, we found that the area immediately lateral to PTg human DTg. (the primate pars dissipata and the rodent retrorubral nucleus) in all three species is only lightly stained for AChE. These findings suggest that the primate PTg pars dissipata is the Posterodorsal Tegmental Nucleus homologue of the rodent retrorubral nucleus and this could warrant a name change in both cases. However, there are The posterodorsal tegmental nucleus (PDTg) has dozens of articles in the literature in which the retrorubral fields been identified by Huang et al. (1992) on the basis of (A8 dopamine cell group) have been mistakenly named as the chemo- and cytoarchitecture (Figures 8.38–8.41). The ‘retrorubral nucleus.’ To avoid this confusion, we recommend nucleus is distinguished by strong AChE reactivity. that the retrorubral nucleus be renamed the ‘retroisthmic nucleus’ since it lies immediately caudal to the caudal boundary of the isthmus. The retroisthmic nucleus is therefore defined as Laterodorsal Tegmental Nucleus an area in 1 between the PTg medially, and the lateral lemniscus and its nuclei laterally. Dorsal to it is the The laterodorsal tegmental nucleus (LDTg) borders microcellular tegmental nucleus of the isthmus, and rostral to it the locus coeruleus and the DTg through some of its is the caudal (isthmic) pole of the substantia nigra.’’ course (Figures 8.42–8.50). It outdistances the DTg caudally and especially rostrally where its ventral part The compact part of human PTg contains persists until DTg compact part is fully displayed strongly AChE-positive cells and neuropil and rides the (Figure 8.43). In humans, as in the rat, the ventral part dorsal aspects of the superior cerebellar peduncle of the LDTg (LDTgV) consists of AChE-positive cells (Figures 8.48–8.53). It has cholinergic and substance-P- that extend into the fibrous tegmentum ventral to PAG. positive cells (see Chapter 34). Kasashima et al. (1998) The LDTgV mingles rostrally with PDTg. LDTg cells have also shown choline acetyltransferase mRNA in are extremely AchE-positive but are usually concealed human PTg neurons. by the intense AChE neuropil of the nucleus. Choline In Figure 8.52, directly medial to the spinothalamic acetyltransferase mRNA has also been shown in tract there is an area of AChE reactivity. Olszewski and human LDTg (Kasashima et al., 1998). Substance P Baxter outlined two nuclei in this position: the subcunei- immunoreactivity is displayed by nearly all the large form and the diffuse pedunculotegmental. We believe cells of the nucleus (Del Fiacco et al., 1984; Nomura that their scheme is not entirely correct, but we cannot et al., 1987). at present make another proposal. This region is prob- ably transversed by ascending AChE fibers of the PTg. Pedunculotegmental Nucleus Riley (1943), referring to Ziehen (1934), included this region in “area U”. The pedunculotegmental nucleus (PTg) is a promi- nent cholinergic cell group in the rostral hindbrain of the human, monkey, rat, and mouse. Paxinos and Wat- Microcellular Tegmental Nucleus son (2006) and Puelles et al. (2007) have renamed the An extensive parvicellular and AChE-reactive pedunculopontine tegmental nucleus the pedunculo- nucleus was identified medial to the parabigeminal tegmental nucleus (PTg), because pons is not a subdivi- nucleus of the rat (Paxinos, 1983, 1985; Paxinos and sion of the brain in the same subordination as the Butcher, 1986). It was called the microcellular tegmental mesencephalon and rhombencephalon. It is not even nucleus (MiTg). No nucleus of such intense AChE reac- in the same subordination of isthmus, because it tivity is found medial to the parabigeminal of the does not engulf the neuroaxis (Puelles et al., 2007). human. However, a parvicellular nucleus of low AChE We reproduce below the argument that Paxinos reactivity is found in a position of the human et al. (2009) have given for renaming the pedunculo- tegmentum analogous to that occupied by the MiTg in pontine tegmental nucleus and for harmonizing the rat. On the basis of these observations, Paxinos the rodent and primate literature by establishing et al. (1990) proposed that the MiTg exists in the human homologies: but has different AChE properties. ‘‘In the human and rhesus monkey, the PTg has been described as having a compact cholinergic part () and a diffuse non-cholinergic part (pars dissipata). In rodents, LOCUS COERULEUS however, Swanson (1992) and Paxinos and Watson (2006) named a non-cholinergic area lateral to PTg as the retrorubral nucleus. The retrorubral nucleus has never been recognized in The locus coeruleus (LC) is a blue-black nucleus con- primates. We suspected that the retrorubral nucleus of the sisting of A6 neurons of Dahlstro¨m and Fuxe. These

III. BRAINSTEM AND CEREBELLUM 310 8. ORGANIZATION OF BRAINSTEM NUCLEI noradrenergic neurons contain neuromelanin. LC is (Klimek et al., 1997). Chemoarchitectonic evidence characterized by large AChE-positive cells (Figures revealed angiotensin II type 1 receptors in the human 8.37–8.49). Meesen and Olszewski (1949) identified in LC (Benarroch and Schmeichel, 1998) and somatostatin the rabbit a ventral extension of the LC, which they in the fetal human LC (Carpentier et al., 1996a, 1996b), called LC alpha. This ventral extension included while the differential decrease in the density of somato- a compact portion and a more extensive diffuse part. In statin-binding sites observed in the fetal LC during the human, Olszewski and Baxter included the compact development supported the notion that the portion of the pars alpha in their LC proper and the somatostatinergic systems in LC as well as in LPB may diffuse part in their subcoeruleus (SubC). Paxinos and be involved in maturation of the respiratory control Watson (1998) labeled the compact part of the LC that (Carpenter et al., 1997). Strong human cocaine- and is ventral to PAG (in the fibrous tegmentum) as -regulated transcript (CART) mRNA subcoeruleus alpha (SubCA). However, the cells more expression was also found in the human LC (Hurd closely resemble those of the LC rather than those of and Fagergren, 2000). The subcoeruleus nucleus is the the SubC; hence, the term “LC alpha” rather than AChE-positive area dorsolateral to the central tegmental “SubC alpha” is used in the present description. Unlike tract (ctg). LC, which has relatively few spinal-projecting cells, the LC alpha exhibits numerous descending projections to the spinal cord as well as many ascending projections RAPHE NUCLEI to the forebrain (W R. Mehler, unpublished observations; Satoh et al., 1977). There is strong NPY mRNA expres- Raphe nuclei are located in the midline, along the sion in the LC (Pau et al., 1998). High concentration of rostrocaudal extension of the brainstem in humans somatostatin-binding sites in the area also indicates pres- (Olszewski and Baxter, 1954). They include the raphe ence of somatostatin receptors in the LC (Carpentier obscurus and raphe magnus nuclei, median and para- et al., 1996a, 1996b). In Aizheimer disease the LC sustains median raphe nuclei, raphe pontis nucleus, and dorsal degeneration, but the LC alpha remains unaffected (Mar- raphe nucleus, and consist mostly of serotonergic cyniuk et al., 1986a, 1986b). Human LC neurons have neurons. Studies in experimental animals have shown been shown to contain glial cell line-derived neurotro- that raphe nuclei in the isthmus and rostral hindbrain phic factor (GDNF) and dopamine-beta hydroxylase mainly project to the , , amygdala, immunoreactivity, norepinephrine transporters (Ordway hypothalamus, cerebellum, and other brainstem nuclei et al., 1997), somatostatin (Carpentier et al., 1997)and such as LC. The raphe nuclei of the rostral hindbrain angiotensin II type 1 receptors. High densities of cortico- are considered to regulate the sleep–wake cycle, tropin-releasing hormone immunoreactive have mood, and ; those in the caudal hindbrain also been shown here (Austin et al., 1997). are related to pain control (Sasaki et al., 2008). Those in the caudal hindbrain mainly project to the spinal Epicoeruleus Nucleus cord.

Unlike the rat, LC of humans confines itself to the Raphe Obscurus and Magnus Nuclei ventrolateral corner of PAG and does not cling to the full dorsoventral extent of the mesencephalic tract of The raphe obscurus (ROb) possesses AChE-positive the trigeminal (Paxinos et al., 1990). In humans, the cells and dendrites which form two paramedian bands space dorsal to the LC and medial to the mesencephalic at the divided midline medial to the medial longitu- tract of the trigeminal nerve is occupied by a group of dinal fasciculus and the predorsal bundle (Figures medium cells, which Paxinos and Huang (1990) called 8.15–8.30). the “epicoeruleus nucleus” (EC) (Figures 8.40–8.48). In Human ROb neurons show immunoreactivity for transverse section this nucleus has the shape of an isos- serotonin (Paterson and Darnall, 2009), substance P celes triangle, with the base resting on the LC and (Del Fiacco et al., 1984; Halliday et al., 1988a; Rikard- a small-angle apex pointing dorsally. EC is best seen Bell et al., 1990) , galanin (Blessing and Gai, 1997), neuro- caudal to the caudal pole of DTg. It remains to be deter- kinin A and B (Covenas et al., 2003), met-enkephalin mined whether EC is a separate entity from the medial (Covenas et al., 2004), and nicotinic acetylcholine parabrachial nucleus. receptor (Duncan et al., 2008). Pathology of major depression was shown to be The raphe magnus (RMg) caps the medial lemniscus accompanied by altered norepinephrine transporter and is most prominent at the rostral pole of the inferior (NET) function (a membrane protein responsible for olive (Figures 8.29–8.34). At this level the raphe (the termination of the action of synaptic norepinephrine midline) is wide and colonized by two parallel chains and a site of action of many ) in LC of pontine nuclei (pararaphales nucleus). Cells of RMg

III. BRAINSTEM AND CEREBELLUM RAPHE NUCLEI 311 tend to be oriented mediolaterally. The RMg neuropil The MnR is found dorsal and rostral to RTg in the shows medium AChE reactivity and is interrupted by rostral rhombomeres and isthmus (Figures 8.44–8.51). the AChE-negative fibers of the medial lemniscus. Rostrally, MnR is limited by the decussation of About half of the raphe magnus cells are positive for the superior cerebellar peduncle. Dorsal to the serotonin and it is possible that serotonin cells are also decussation, the nucleus merges with the caudal linear AchE-positive. Approximately 30% of serotonin cells nucleus. in RMg also contain substance P in humans (Halliday Human PMR contains corticotropin-releasing et al., 1988a). In the rat, serotonergic cells in the RMg hormone-immunoreactive fibers (Austin et al., 1997). and adjacent nucleus gigantocellular reticular nucleus MnR neurons contain GABA-B receptor mRNA, co- are likely involved in modulation of nociceptive trans- localized with serotonin transporter receptors in rats mission, whereas non-serotonergic cells modulate stim- (Serrats et al., 2003). Some MnR neurons contain ulus-evoked or alerting as well as spinal substance P (Baker et al., 1991b). autonomic motor circuits involved in and sexual function (Mason, 2001). Raphe Pontis Nucleus RMg has connections mainly to the periaqueductal Unlike other raphe nuclei, the cells of raphe pontis gray and the spinal cord, suggesting its involvement in nucleus (RPn) are not serotonin-positive (Figures 8.32– (Hornung, 2004). There are also gender 8.36). McKinley et al. in Chapter 18 observes that in differences in RMg, with females containing more a narrow the raphe pontis nucleus is, in fact, the neurons than males, and males showing a higher caudal pole of MnR and proposes to abandon the term proportion of large multipolar and fusiform, but not of “raphe pontis nucleus” as referring to a region ovoid neurons (Cordero et al., 2001). harboring serotonin neurons. We maintain this cell group and assume it is the homolog of the raphe pontis found in rhombomere 4 in the rat. McKinley et al. Median and Paramedian Raphe Nuclei describe this cell group in detail in Chapter 18. In the rat, Paxinos and Watson (1998) used the term Dorsal Raphe Nucleus median raphe (MnR) to describe the midline nucleus containing large cells that are predominantly serotonin- The dorsal raphe nucleus (DR) shows extreme AChE positive. The MnR cells differ from the remaining reactivity in the neuropil of its wings (Figures 8.37–8.57). cells in what was formerly called the central superior The median strip of cells is associated with less reac- medial nucleus (the region between the tectospinal tivity in the neuropil; consequently the cells, which tracts) in terms of morphology, chemoarchitecture, display medium reactivity can be visualized. An autora- and connectivity. Paxinos and Watson abandoned diography study showed that neurons of dorsal raphe the term “central superior medial nucleus” because are characterized by NPY mRNA expression (Pau this nucleus actually encompasses two heterogeneous et al., 1998). Hurd and Fagergren (2000) reported strong nuclei. Taking Mehler’s suggestion, Paxinos and human CART mRNA expression in the DR, though it is Watson (1998) introduced the term “paramedian not clear whether the message is in serotonin-containing raphe nucleus” (PMR) to refer to the more laterally cells. located non-serotonergic cells, which are distinct DR neurons are not only confined to the midline, from MnR (see their Figures 48–51). but extend laterally into the ventral periaqueductal In the human, the distribution of serotonergic cells is gray and surround the medial longitudinal fasciculus. much more extensive than that of the rat. However, The caudal part of the dorsal raphe nucleus (DRC) many (but not all) laterally located serotonin cells of consists of a narrow double string of cells extending the human morphologically resemble the remainder of caudally up to the level of the abducens nucleus. The the reticular formation cells and do not present a specific rostral end of DR neurons has been shown to have dendritic orientation. The serotonin cells of MnR are a similar morphology with those of CLi (Hornung, characterized by their lack of laterally oriented 2003). dendrites. In the rat, an intense AChE-positive zone Human DR neurons have been shown to contain separates MnR from PMR. In humans, a similar AChE- substance P, with a 40% co-localization with serotonin positive zone shepherds the large median raphe cells (Baker et al., 1991b). Serrats et al. (2003) observed rostrally but is invaded by the larger midline cells GABA-B receptor mRNA containing neurons in human caudally (Paxinos and Huang, 1995). The shepherding DR; 85% of these also contain serotonin transporter zone, as well as MnR and PMR, display bowed bound- mRNA. A high density of radioligand binding to norepi- aries that collectively give this region the appearance nephrine transporters is also found in DR (Ordway of a barrel with staves. et al., 1997).

III. BRAINSTEM AND CEREBELLUM 312 8. ORGANIZATION OF BRAINSTEM NUCLEI

VENTRAL MESENCEPHALIC to the superior cerebellar peduncle as the peduncle TEGMENTUM AND SUBSTANTIA NIGRA encapsulates the red nucleus (Figures 8.57–8.64).

Chapter 13 gives a comprehensive pictorial represen- Retrorubral Fields tation of the mesencephalic dopamine groups on the basis of tyrosine hydroxylase immunoreactivity. The dopamine-containing (tyrosine-hydroxylase- positive) retrorubral fields are found caudal and dorsal Caudal Linear Nucleus to the caudal pole of the red nucleus, at the level where the third nerve forces its way through the red nucleus. The caudal linear nucleus (CLi) is more extensive in In drawing the borders of the human retrorubral fields the human than in the rat (Figures 8.52–8.56). In it may be useful to consider the map of the pigmented humans, it extends from the medial longitudinal cells in the human brainstem presented by Mai et al. fasciculus dorsally to the interfascicular nucleus (1997). ventrally. Caudally, it rides on the rostral aspect of the decussation of the superior cerebellar peduncle until it joins the rostral tip of MnR. Some CLi cells Paranigral Nucleus infiltrate the decussation of the superior cerebellar In contrast to the rat, the paranigral nucleus (PN) of peduncle to mingle with the median raphe. The humans is extremely AchE-reactive and abuts not on caudal linear nucleus consists of a median and two the interpeduncular nucleus as in the rat but on the paramedian corridors of cells that are strikingly medial pole of the substantia nigra (Figures 8.52–8.55). different in their chemoarchitecture. The median Del Fiacco et al. (2002) observed many glial cell line- corridor is AchE-negative and contains serotonergic derived neurons in the human substantia nigra, paranig- neurons, while the lateral corridors are AchE-positive ral nucleus, and the region immediately dorsal to it. and contain numerous tyrosine-hydroxylase-positive These regions are considered to belong to the human cells. counterpart of the rodent A10 cell group (Pearson Paxinos and Huang (1995) named the unpaired et al., 1990). midline corridor featuring the serotonin cells – the azygos part of CLi. This azygos part succeeds MnR (with which it is continuous through cell bridges Parabrachial Pigmented Nucleus blasting through the superior cerebellar peduncle). The parabrachial pigmented nucleus (PBP) occupies The AChE-positive catecholaminergic corridor is the the space between the substantia nigra compact part zygos part of CLi. The paramedian clusters do not and the red nucleus (Figures 8.52–8.64). It is character- extend as far caudally as the median cluster; thus, it ized by AChE-positive neurons and a neuropil of is only the median cluster that meets MnR. The CLi medium to dense reactivity. borders the rhomboid nucleus and is succeeded rostrally by the rostral linear nucleus at approxi- mately the point of the caudal pole of the red Substantia Nigra nucleus. The substantia nigra (SN) displays intense AChE reac- tivity in the cell bodies and neuropil of its compact (SNC) Interfascicular Nucleus and lateral (SNL) parts (Figures 8.52–8.64). In places The interfascicular nucleus (IF) straddles the interpe- SNC divides or envelopes the reticular part. The duncular nucleus. Laterally, the IF is in contact with the dopamine-containing neurons are AchE-positive but paranigral nucleus. In contrast to rats, cats, and are not cholinergic (Butcher and Talbot, 1978). The monkeys, in which the IF is a median cluster, the human reticular part of SN is less reactive than the compact IF is small and consists of two paramedian clusters that part. Damier et al. (1999a) divided human SN into are connected only by cell bridges (Halliday and To¨rk, a calbindin-rich region (matrix) and five calbindin-poor 1986). Compared to other nuclei of the ventral mesence- nigral subdivisions (nigrosomes). For a comprehensive phalic tegmentum, it has significantly smaller cells description of SN, see Chapter 13. (Halliday and To¨rk, 1986). Both the cells and the neuro- Substance P (Gibb, 1992), thyrosine hydroxilase pil are densely AchE-positive. (Damier et al., 1999a), and GABA-immunoreactive neurons (Petri et al., 2002; Waldvogel et al., 2004), and Rostral Linear Nucleus tyrosinase mRNA (Xu et al., 1997) have been observed in human SNC. Calbindin-positive neuropil is found The rostral linear nucleus (RLi) consists of scattered throughout the reticular part of SN and most of the pigmented AChE-reactive cells within and dorsomedial SNC (Damier et al., 1999a).

III. BRAINSTEM AND CEREBELLUM CRANIAL MOTOR NUCLEI 313

The most striking neuropathologic finding in Parkin- with this in the monkey (Satoda et al., 1987). For more son’s disease is a progressive loss of dopaminergic information on the nucleus, see also Chapter 9. neurons in SNC. The loss of dopamine-containing The stylohyoid part of the facial nucleus (7SH) is found neurons is significantly higher in the nigrosomes when above the caudal half 7N. It assumes a compact pyramidal compared to the calbindin-rich matrix (Damier et al., shape at its rostral pole immediately medial to the exiting 1999b). facial nerve (Figure 8.32). The accessory 7N are intensely reactive for AChE. Surrounding the 7N is an AChE-posi- Interpeduncular Nucleus tive zone which was named the perifacial zone in the The interpeduncular nucleus (IP) displays an AChE- human and the brain (Paxinos and Huang, 1995). dense zone that straddles a core of medium reactivity (Figures 8.51–8.61). This pattern is not readily compa- Motor Trigeminal Nucleus rable to that shown in the rat. IP has been implicated in sleep regulation (Herkenham, 1991), pain sensitivity The caudal pole of the motor trigeminal nucleus (Meszaros et al., 1985), and active avoidance behavior appears medial to the exiting root of the facial nerve (Hammer and Klingberg, 1990). Panigrahy et al. (1998) (Figure 8.33). It extends rostrally to the dense caudal observed high muscarinic receptor binding in the pole of LC. The motor trigeminal nucleus is strongly lateral, high serotonergic binding in the dorsal, and active for AChE (cells and neuropil) and the reactivity high opioid receptor binding in the medial subdivisions extends into the cell-poor peritrigeminal zone (Paxinos of IP in humans. and Huang, 1995)(Figures 8.36, 8.37). As in the rat, the fasciculus retroflexus in humans displays an AChE-dense core surrounded by an AChE-negative area. Abducens Nucleus The abducens nucleus (6N) is located ventral and caudal to the horizontal limb of the exiting facial nerve CRANIAL MOTOR NUCLEI (Figures 8.31–8.33). The 6N consists of large motoneu- rons and small multipolar . It has prominent Hypoglossal Nucleus AChE-positive cells but its neuropil is only of medium intensity. The nucleus is also discussed in Chapter 9. The hypoglossal nucleus (12N) is one of the most AChE-reactive nuclei in the staining of both cell bodies and neuropil (Figures 8.14–8.25). Its caudal representative Trochlear Nucleus is the ventrolateral division (I2VL). This division possesses large AChE-positive neurons found within the fibrous The trochlear nucleus (4N) is found in an invagina- zone ventrolateral to the central canal, at the medial border tion of the medial longitudinal fasciculus near the level of MdV (see above). As in the rat (Krammer et al., 1979), of the junction of the inferior and superior colliculi the I2VL disappears as soon as the dorsal division (Figures 8.53–8.55). Its motoneurons are AchE-positive develops. In the rat, the 12VL innervates the geniohyoid but its neuropil is only moderately reactive. The 4N is muscle (Krammer et al., 1979). The ventromedial division separated from the rostrally lying oculomotor nucleus of 12N is the largest, and in the rat it innervates the genio- by a small cell-free space. The two nuclei can be distin- glossus muscle (Krammer et al., 1979). We are not confi- guished by the fact that 4N is embedded in the dent about the homology of the dorsal division because fasciculus while the oculomotor nucleus is cradled in it. another subnucleus (potentially a laterally displaced At the caudal pole of the trochlear nerve the midline dorsal division) appears in the human. In the rat, the between the two medial longitudinal fasciculi features dorsal division innervates the styloglossus and hyoglos- a dense AChE segment (Paxinos et al., 1990). This may sus muscles. The nucleus of Roller accompanies the rostral correspond to the parvicellular “compact interfascicular third of the hypoglossal nucleus (Figures 8.21–8.25). nucleus” (CIF) of Olszewski and Baxter (1954).

Facial Nucleus Oculomotor Nucleus The facial nerve nucleus (7N) abuts the rostral end of Olszewski and Baxter (1954) report that the oculomotor IRt and persists until the level of the exiting facial nerve nucleus (3N) is approximately 5 mm long. It extends from (Figures 8.31–8.34). In humans, as in the rat, the 7N the trochlear nucleus to the unpaired anterior portion of contains AChE-reactive cell bodies and neuropil. Subdi- the nucleus of Edinger-Westphal (EW) (Figures 8.56– vision of the 7N in the human (see Figures 8.31–8.34) 8.58). The caudal pole of the oculomotor nucleus is more (Pearson, 1947; Paxinos and Huang, 1995) is in conflict reactive for AChE than the trochlear nucleus.

III. BRAINSTEM AND CEREBELLUM 314 8. ORGANIZATION OF BRAINSTEM NUCLEI

EW is originally described as a cytoarchitecturally column nuclei (Figures 8.16–8.24). Paxinos and defined cell group considered as the location of pregan- colleagues (1990) named this zone the “medial pericu- glionic neurons of the . However, recent neate nucleus.” This basal zone features small, medium, sudies suggest that EW has come to indicate different and occasionally large neurons that are AchE-positive. nuclei in different species. It is reactive for AChE in The most medial part of this zone interposes itself both its cells and neuropil (Figures 8.58, 8.59). between EC, solitary, and interpolar spinal trigeminal nuclei. This medial (basal) pericuneate zone (MPCu) SOMATOSENSORY SYSTEM was included in Cu by Olszewski and Baxter (1954), even though it can be seen in their photomicrographs to be separate from Cu proper and possesses smaller Gracile Nucleus cells (their plates 10 and 11). At levels caudal to the At the level of the pyramidal decussation, the obex, cells in MPCu are diffuse and smaller. Rostral to tapering caudal pole of the gracile nucleus (Gr) appears the level of the area postrema (about 1 mm from the as small clusters of AChE-positive cell bodies. Rostrally, obex) these cells increase in number and become more the main body of Gr appears with the characteristic heterogeneous in size and shape. At one point, MPCu patches of AChE reactivity corresponding to clusters cells appear as a triangular mass that merges rostrally of cells separated by AChE-negative myelinated fibers with large, rounder cell clusters (Figures 8.17–8.24). (see Chapter 25). The Gr persists almost to the rostral A comparable cell cluster is shown by Olszewki and pole of the area postrema (Figure 8.19). Baxter in their plates 12 and 13, lateral to the solitary nucleus and medial to the spinal trigeminal nucleus. In Cuneate Nucleus AChE-stained sections, other small AChE-positive cells extend into the pale neuropil capping the oral pole of The cuneate nucleus (Cu) first appears at midlevels of Cu (Figure 8.22). This basal MPCu is coextensive in the pyramidal decussation (Figure 8.7) and extends to length with 12N. There is no basal region ventral to the rostral pole of the area postrema (Figure 8.21). The the gracile nucleus, except for a few clusters at its oral Cu displays patches of AChE reactivity similar to those pole. of Gr but of higher intensity. Attached to the borders of some compact bundles of the cuneate fasciculus are clus- Lateral Pericuneate Nucleus ters of large cells that are well stained for Nissl (density Lateral and ventrolateral to the external cuneate near the brain surface on the border with the gracile nucleus there are variably shaped aggregates of chiefly nucleus in Figure 8.19). The neuropil of these clusters large AChE-positive neurons intercalated in the medial is extremely reactive for AChE. It seems to correspond edge of the inferior cerebellar peduncle. The most prom- to the area reported to contain substance P fibers by inent group of these cells frequently forms a wedge Del Fiacco et al. (1984) and Covenas et al. (2003). separating the cuneate fasciculus from the dorsal part of Sp5. This chain of cells extends from the level of the External Cuneate Nucleus obex to the oral pole of ECu (Figure 8.22), equivalent in length to the hypoglossal cell column. This cell group Unlike other species, the human external cuneate was described by Ziehen (1934) as the “promontorium” nucleus (ECu) occupies a greater area of the medulla (, “to jut out”) and was considered part of the than Cu or Gr (Figures 8.13–8.25). It features large cells insular nuclei of ECu by Olszewski and Baxter (1954, heavily stained for AChE on a pale background. It their plate 10). This nucleus has been confused with expands at the level of the obex and becomes the largest nucleus X (described below). Paxinos and colleagues of the rostral to the obex (1990) have called it the “lateral pericuneate nucleus”. (Figure 8.22). At its rostral pole it narrows and is found Both the lateral pericuneate (LPCu) and medial pericu- between the mediodorsal aspect of the inferior cerebellar neate (MPCu) nuclei were identified as separate but peduncle, the spinal vestibular nucleus, and the spinal related entities by Braak (1971). Braak adopted Ziehen’s trigeminal nucleus. It terminates short of the rostral (1934) term “promontorium” for the lateral group and pole of 12N (Figure 8.25). coined the term “repagulum cuneati” (Greek, pagus, “something fixed or fastened together”) for the medial Pericuneate, Peritrigeminal, X, and group of cells basal to Cu. Paratrigeminal Nuclei Peritrigeminal Nucleus Medial Pericuneate Nucleus The peritrigeminal nucleus (Pe5) is in places contin- At the level of the obex, a narrow zone of pale AChE uous with LPCu and is found lateral, ventral, and reactivity appears in the neuropil ventral to the dorsal medial to Sp5. Caudally, it commences at the level of

III. BRAINSTEM AND CEREBELLUM SOMATOSENSORY SYSTEM 315 the caudal pole of the dorsal accessory olive and extends vestibular nucleus (SpVe) give rise to a third vestibulospi- to the rostral pole of 12N (Figures 8.15, 8.16). Olszewski nal pathway (see review by Mehler and Rubertone, 1986). and Baxter (1954) included the lateral segment of Pe5 in The ascending spinal fibers that delineate both the lateral their insula cuneati lateralis (their plate 10). The ventral X group and the medial basal column nuclei also appear part of Pe5 is usually found between Sp5 and the subtri- to make connections with group F-like cells at this level of geminal LRt. At times, however, it is found ventral or transition between the oral pole of the cuneate nuclei and lateral to the subtrigeminal nucleus. A ventromedial the caudal pole of the vestibular nuclei. cluster that receives anteroventral quadrant fibers has been labeled the paravagal nucleus by Braak (1971) Nucleus X (small-celled nucleus between the labels Amb and IRt). Sadjadpour and Brodal (1968) identified nucleus X as The Pe5 has a medial extension that intercedes between a cell group related to the dorsal boundary of SpVe, Sp5 and the LRt. extending from the rostral level of ECu to the caudal A distinct ascending neuronal projection from the level of the dorsal cochlear nucleus. They describe thermoreactive cells of the peritrigeminal nucleus to nucleus X as a small triangular area just medial to the the thermoreactive cells of the medial preoptic nucleus inferior cerebellar peduncle, featuring small, lightly has recently been described in rats by Bratincsak et al. stained cells. Paxinos and Watson identified nucleus X (2008). in The Rat Brain in Stereotaxic Coordinates (Paxinos and Watson, 1998) as the AChE-reactive rostral continuation Afferent Connections of the Pericuneate of ECu. We observed a similar AChE-reactive cluster of and Peritrigeminal Nuclei small cells in the position described by Sadjadpour and In experimental animals, the pericuneate and Pe5 Brodal. Larger cells invade or form a boundary around receive ascending anterolateral spinal quadrant fiber nucleus X and these cells may belong to SpVe (Sadjad- connections (via the inferior cerebellar peduncle) and pour and Brodal, 1968). We believe that the ventral do not receive dorsal root primary fibers (Mehler, part (between the spinal vestibular nucleus and the infe- 1969). Nucleus X and the paratrigeminal nucleus (Pa5) rior cerebellar peduncle) is different from SpVe, but we project to the cerebellum (Mehler, 1977; Somana and have not grouped it with nucleus X because of the larger Walberg, 1979). The MPCu cells may receive afferents cells of this area and its poorer AChE reactivity. Nucleus from the same ascending fiber system that projects to X can be confused with the insulae cuneati lateralis of LPCu. Cervical dorsal root connections to the pericu- Olszewski and Baxter (our lateral pericuneate nucleus). neate cells cannot be ruled out. Cortical input to the If we accept Sadjadpour and Brodal’s view, nucleus X is basal dorsal funicular nuclear region has been verified unlikely to extend this far ventrally (Figures 8.26, 8.27). in humans (Kuypers, 1960); rubrobulbar connections In addition, LPCu has large cells whereas nucleus X, with the region have also been described (Holstege according to Sadjadpour and Brodal, has small cells. and Tan, 1988). The MPCu cells are believed to have connections with the overlying dorsal column nuclei Paratrigeminal Nucleus that function as an intermediate zone (Kuypers and In the rat, the paratrigeminal nucleus (Pa5) forms Turek, 1964). Differential studies of retrograde cell a crescent between the spinocerebellar tract and the labeling, following HRP injections into the ventral poste- spinal tract of the trigeminal, usually invading the latter. rior lateral thalamic nucleus, demonstrated that many The Pa5 of the rat features small cells and is character- cells in the medial basal pericuneate zone (PCu) that ized by light AChE and dense substance P reactivity. convey tactile information also project to the thalamus Some of its cells are substance P positive (Chan-Palay, through the medial lemniscus with gracile and cuneate 1978a, 1978b). While we accept Chan-Palay’s definition axons. However, Ostapoff et al. (1988) have concluded of this nucleus in the rat, we disagree with her on the that what might be the homologs of the PCu cells in human homolog of the Pa5. She considers the insulae the racoon relay deep subcutaneous kinesthetic sensa- cuneati lateralis of Olszewski and Baxter to be the Pa5 tions ending chiefly in the ventral intermediate (Vim)- of the human. Paxinos and colleagues (1990) have like shell region rostral to the tactile thalamic nucleus. grouped the dorsal insula cuneati lateralis with LPCu They also confirmed that the caudally situated cells of and the ventral insula with the peritrigeminal zone. subgroup X project to the cerebellum, but cells they They suggested that the human Pa5 may be, in fact, identified as rostrally situated subgroup X, like nucleus a string of cells contained primarily within the spinal Z, also project to the thalamic shell region. tract and based their parcellation on the basis that the In animal experiments, cells capping the oral pole of Pa5 of the rat has small cells in agreement with the par- Cu project to the cerebellum and do not join the medial vicellular clusters within the human spinal tract and in lemniscus (Mehler, 1977). Vestibular group F-like cells contradistinction to the lateral pericuneate zone, which (FVe) intercalated in the ventral caudal pole of the spinal has large cells. An inconsistency in the homology is

III. BRAINSTEM AND CEREBELLUM 316 8. ORGANIZATION OF BRAINSTEM NUCLEI that the Ad reactivity of proposed Pa5 of the human is the medial lemniscus. The islands appear just rostral to lower than that displayed in the rat. the caudal pole of the principal nucleus of the inferior olive. Caudally, they are wholly confined within the Spinal Trigeminal Nucleus medial lemniscus. However, rostrally they unite and flank the lateral side of the medial lemniscus. These cell groups The caudal spinal trigeminal nucleus (Sp5) is charac- resemble the medial accessory olive but are clearly more terized by strong AChE reactivity in the superficial medial to it. Given their position, Paxinos et al. (1990) layers, including the substantia gelatinosa. The marginal called them the “endolemniscal nucleus.” This nucleus zone of the caudal part of Sp5 can be distinguished has no equivalent in the rat and not even in the chim- because it is less AchE-reactive than the gelatinous panzee (Paxinos and Huang, unpublished observations). nucleus but more than the spinal tract. Some AChE-reac- tive cells are found totally within the cuneate fasciculus, yet strong AChE reactivity suggests that they most likely B9 and Supralemniscal Nucleus belong to the gelatinous part of the caudal Sp5 rather then to the cuneate system. Also, NPY mRNA expres- The B9 is identified as a group of serotonergic cells sion was found within this nucleus (Pau et al., 1998). lying above the medial lemniscus (Figures 8.38–8.48). The oral Sp5 (Sp5O) has a concentric pattern of AChE This cell group also contains a region of extremely reactivity with an extremely AChE dense core (Figures strong AChE reactivity that is distinguished as the 8.31–8.35). It is succeeded rostrally by the less reactive supralemniscal nucleus (SuL; Figures 8.36–8.46). principal sensory nucleus of the trigeminal nerve. In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small patches adulterated by VESTIBULAR NUCLEI negative areas. In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small There are four components of the vestibular nuclear patches adulterated by negative areas. The interpolar complex: the superior, medial, lateral, and inferior nucleus (Sp5I) displays moderate AChE reactivity, (spinal) vestibular nuclei. The vestibular nuclei receive although there are occasional extremely intense patches afferents from the labyrinth of the inner , from the that correspond to parvicellular regions (Figures 8.16– spinal cord and the reticular formation. Efferents from 8.30). In the ventral part of the nucleus a rodlike struc- the vestibular nuclei pass through the inferior cerebellar ture appears (circular in cross-section), featuring small peduncle to reach the flocculus and nodule, and some compact neurons and extremely AChE-dense neuropil. form the vestibulospinal projections that descend in No such structure appears in the rat. Both Sp5O the ventral funiculus of the spinal cord. and Sp5I are reported to contain significant numbers of somatostatin receptors as revealed by somatostatin- binding sites (Carpentier et al., 1996). In humans, Medial Vestibular Nucleus Sp5 neurons have been shown to contain serotonin, The medial vestibular nucleus (MVe) succeeds the calcitonin gene-related peptide, and substance P (Smith gracile nucleus rostrally at the level at which the gelati- et al., 2002), bombesin (Lynn et al., 1996), glial cell nous solitary nucleus is most prominent and persists line-derived neurotrophic factor (GDNF) (Del Fiacco rostrally to the level of the abducens nucleus (Figures et al., 2002), met-enkephalin (Covenas et al., 2004), 8.22–8.33). It has a mottled appearance in AChE. neurokinin (Covenas et al., 2003), and parathyroid Caudally, embedded in the medial part of MVe, are hormone receptor 2 (PTH2R) (Bago et al., 2009) two clusters of larger cells, the neuropil of which stains immunoreactivities. strongly for AChE (Figure 8.22). It is important to point out that a group of large neurons positioned ventrally Mesencephalic Trigeminal Nucleus and medially to the main body of MVe is currently The mesencephalic nucleus of the trigeminal nerve considered to be part of the medial rather than lateral (Me5) features prominent AChE-reactive cells and, as vestibular nucleus, as it was previously thought. in the rat, its cells and axons form a thin sheet that forms the lateral border of cylindrically shaped periaqueductal Spinal Vestibular Nucleus gray (PAG) (Figures 8.35–8.61). The spinal vestibular nucleus (SpVe) overlaps the Endolemniscal Nucleus rostral pole of the external cuneate and subsequently replaces it (Figures 8.21–8.31). It is rectangular in cross- At caudal medullary levels, long islands of cells section and is located dorsolateral to the solitary strongly reactive for AChE separate dense fascicles of and spinal trigeminal nuclei. The SpVe is characterized

III. BRAINSTEM AND CEREBELLUM AUDITORY SYSTEM 317 by the passage of the lateral vestibulospinal tract conspicuous feature of superior olive in Nissl prepara- which, being AchE-negative, contrasts with the medium tions is the medial superior olive (MSO). It consists of density of the neuropil of the SpVe. Distribution of medium-sized, slightly AChE-positive cells and is sur- somatostatin binding revealed that both MVe and SpVe rounded by AChE-positive vascular elements that are contain numerous somatostatin receptors (Carpentier themselves encircled by an AChE-negative zone. The et al., 1996). The area above the spinal and dorsal vestib- lateral superior olive is extremely negative in AChE prep- ular nucleus is identified as the paravestibular nucleus. aration but features some moderately stained . Nucleus Y is allocated a real-estate above the inferior A conspicuous characteristic of the lateral superior olive cerebellar peduncle prior to ascendance of the peduncle is its significantly greater size relative to the size of the to the cerebellum. entire superior olive nucleus in the rat or the mouse. The periolivary nuclei surround the superior olive. Lateral Vestibular Nucleus The dorsal periolivary nucleus (DPO) is the most AChE-reactive structure in the superior olive complex. The lateral vestibular nucleus (LVe) replaces SpVe The position of the dorsal periolivary nucleus is betrayed rostrally (Figures 8.30, 8.31). It displays large AchE-posi- by MSO, which points directly to it (Figures 8.32–8.34). tive cells and has lighter neuropil than the rest of the The dorsal periolivary nucleus probably contains the vestibular nuclei. The superior vestibular nucleus is bulk of the cells that provide the cochlear efferents. The not optimally displayed in our plates. human homologs of the medioventral (MVPO) and later- oventral periolivary nuclei (LVPO) are AchE-positive. The human homolog of the superior paraolivary Interstitial Nucleus of the Eighth Nerve nucleus remains an enigma. In the rat, this nucleus is The eighth nerve is AchE-negative but its interstitial contiguous with MSO. In the human, at this position, nucleus displays AChE-positive cell bodies and we noticed a vertically oriented stream of cells. These neuropil. cells are medium-sized and AchE-positive, but do not display the dense AChE neuropil that characterizes the dorsal paraolivary nucleus. Judging from the maps of Nucleus of Origin of Vestibular Efferents retrogradely labeled cells following HRP injections into The nucleus of origin of vestibular efferents is identi- the cat cochlea, these cells may also belong to the cholin- fied by its proximity to the genu of the seventh nerve by ergic efferent projection. Paxinos and Watson (1998). In the human, as in the rat, Our lateroventral periolivary nucleus (LVPO) is the the nucleus is distinguished as a group of AchE-positive ventral nucleus of the trapezoid body of Kulesza neurons riding on top of the horizontal limb of the root (2008), and our medioventral periolivary nucleus of the seventh nerve. (MVPO) plus nucleus of the trapezoid body (Tz) is the medial nucleus of the trapezoid body. For a comprehen- sive account of the human auditory system and superior AUDITORY SYSTEM olive, see Chapter 36.

Ventral and Dorsal Cochlear Nuclei Trapezoid Nucleus Cochlear fibers originating from the spiral ganglion Identification of the human homolog to the trapezoid terminate on the ventral and dorsal cochlear nuclei. nucleus (Tz) has been elusive. Stromberg and Hurwitz The ventral cochlear nucleus (VC) displays AChE-posi- (1976) and Richter et al. (1983) suggested tentatively tive cell bodies against a light neuropil. It can be distin- that an attenuated homolog of Tz in the human at the guished from the pontobulbar nucleus, which is located level of the exiting trochlear nerves. Indeed, Paxinos more medially and which displays high AChE activity and colleagues (1990) found Tz at the level of the exiting in its neuropil. The VC also features a cap that is slightly sixth nerve in the shape of a golf club, with most of its reactive in the neuropil. The dorsal cochlear nucleus is cells underlying the central tegmental tract and more reactive in AChE preparations than VC. At the bordering the medioventral periolivary nucleus. The same time the superficial glial zone of the nucleus is cells of Tz are large, with weak AChE reactivity, and less AChE reactive then the nucleus itself. are found among the caudal crossing fibers of the trape- zoid body (Figures 8.33–8.36). It has been pointed out by Superior Olive Paxinos and colleagues (1990) that Tz in the human is much less cellular than in the rat. Met-enkephalin The superior olive is the AChE-poor area rostroventral immunoreactive neurons have been shown in the to the facial nucleus (Figures 8.32, 8.34). The most human Tz (Covenas et al., 2004).

III. BRAINSTEM AND CEREBELLUM 318 8. ORGANIZATION OF BRAINSTEM NUCLEI Nuclei of the Lateral Lemniscus Superior Colliculus The ventral nucleus of the lateral lemniscus (VLL) The laminar pattern and the morphology of the major succeeds the superior olive rostrally (Figures 8.44– cell types of the superior colliculus closely resemble that 8.46).TheVLLcanbedistinguishedfromsuperior found in other species. Laemle (1983) has provided olive by its slightly larger cells and by the fact that a Golgi analysis of the human superior colliculus (SC). the cell group, after tapering to an elongated rostral Morphologically, SC can be divided into: (1) a superficial pole, becomes larger and more cellular. In addition, division consisting of the zonal, superficial, and optic the cells of the VLL are slightly more AchE-reactive layers; (2) an intermediate division consisting of the than those of superior olive. The VLL commences at intermediate gray and white layers; and (3) a deep divi- the level of the oral pole of the motor nucleus of sion consisting of the deep gray and deep white layers the trigeminal. The nuclei of the lateral lemniscus (Figures 8.56–8.62). reach the caudal pole of the pedunculotegmental The AChE reactivity of the human SC resembles that nucleus. For a quantification of the human nuclei of the rat. The superficial gray layer is the most intensely of the lateral lemniscus, see Ferraro and Minckler reactive. The zonal layer is also reactive except for its (1977). most superficial strip. The optic nerve layer shows less reactivity than that of the surrounding superficial and intermediate gray layers and is, as a result, conspicuous. Inferior Colliculus The intermediate gray and white layers show intense reactivity. The intermediate white layer displays peri- As in the rat (Paxinos and Watson, 1998), the inferior odic patches of AChE reactivity as observed in the rat colliculus (IC) of the human displays light AChE reac- (Paxinos and Watson, 2007). Lattices of high cytochrome tivity that features slightly denser patches, especially oxidase or succinate dehydrogenase activity have been in the external cortex (ECIC) (Figures 8.50–8.56). In the observed in the human SC (Wallace, 1988). The anterior central nucleus of IC, blood vessels are visible as wavy is densely reactive for AChE and so is the lines of some AChE positivity. For more details subadjacent parafascicular nucleus. A number of enig- regarding IC, see Chapter 36. matic patches of AChE reactivity appear below SC.

Nucleus of the Brachium of the Inferior Parabigeminal Nucleus Colliculus The parabigeminal nucleus (PBG), while somewhat The nucleus of the brachium of the inferior colliculus inconspicuous in Nissl preparations, is all too evident (BIC) shows pale AChE reactivity, but is recognizable in AChE-stained sections (Figures 8.51–8.54). The because the surrounding dorsolateral tegmentum is human PBG neurons contain choline acetyltransferase AchE-negative (Figures 8.54–8.58). Rostrally, the subbra- (Kasashima et al., 1998) and glial cell line-derived neuro- chial nucleus is found beneath the BIC. trophic factor (GDNF) (Del Fiacco et al., 2002) immunoreactivity.

Medial Geniculate Medial Terminal Nucleus of the Accessory The medial geniculate (MG) displays weak and Optic Tract blotchy AChE reactivity (Figures 8.56–8.62). By The existence of the medial terminal nucleus (MT) of homology with the monkey (Pandya et al., 1994), Paxinos the accessory optic tract is ambiguous in humans. On the and Huang (1995) recognized the AChE-negative ventral basis of observations on the monkey, Fredericks et al. and the AChE-positive medial subnuclei of MG, as well (1988) proposed that MTshould be present in the human as the strongly AChE-reactive and large-celled suprage- at a position transversed by the lateral rootlets of the niculate nucleus. oculomotor nerve. We can not find it in humans.

VISUAL SYSTEM PRECEREBELLAR NUCLEI AND RED NUCLEUS The visual system is covered in detail in Chapter 37, but some elements of the visual pathways represent Chapter 15 includes a comprehensive description of integral structural parts of the brainstem and as such the cytoarchitecture and connectivity of the precerebel- are presented in this chapter. lar nuclei.

III. BRAINSTEM AND CEREBELLUM PRECEREBELLAR NUCLEI AND RED NUCLEUS 319

Inferior Olive Dorsal Accessory Olive Medial Accessory Olive Olszewski and Baxter (1954) and Braak (1970) included in the dorsal accessory olive (IOD) two hetero- AChE is differentially distributed in the medial acces- geneous and discontinuous groups of cells. Paxinos and sory olive. The lateral part of the medial accessory olive, colleagues (1990) reserved the name IOD for the larger the subnucleus A (IOA), displays some of the densest eyebrow-shaped rostral part that caps the dorsomedial AChE reactivity found in the medulla (Figures 8.14– aspects of the principal olive. This persists until the 8.18). Both the neuropil and the cell bodies are densely frontal pole of the olive, where it has the shape of reactive. IOA is the group that appears at the caudal a comma (Figures 8.15–8.30). The smaller, caudal subnu- pole of the olive and, rostrally, greatly outdistances the cleus of the IOD (IODC) is rod-shaped (round in cross- other nuclei of the medial accessory olive. Subnucleus B section) and, compared with IOD proper, has denser (IOB) is slightly less reactive (Figures 8.16–8.18). Subnu- AChE reactivity and features smaller cells. The IODC cleus C (IOC) is less densely stained in the neuropil and commences prior to the principal nucleus and continues the cell bodies are clearly visible. In this respect, it resem- until the linear nucleus becomes very prominent, at bles the beta nucleus that it borders (Figures 8.16–8.18). which point it briefly attains a horizontally oriented spindle shape (Figures 8.15–8.18). It is succeeded by the Beta Nucleus IOD after a small hiatus. Paxinos and colleagues (1990) The beta nucleus (IOBe) in the cat stains poorly for called the posterior part “caudal dorsal accessory olive.” AChE and is confined to the caudal one-third of the olive The inferior olive, including the caudal dorsal accessory (Marani et al., 1977). In the monkey, IOBe disappears olive, was excellently displayed by Kooy (1916). Human prior to the full development of the principal nucleus IOD contains a high density of met-enkephaline-immu- (Brodal and Brodal, 1981). In our human material, noreactive fibers (Covenas et al., 2004). IOBe appears as one of the caudal representatives of the olive but vanishes well before the appearance of Principal Inferior Olive the rostral division of the dorsal accessory olive (Figures The inferior olive principal nucleus (IOPr) shows 8.15–8.18). homogeneous medium staining for AChE neuropil and cell bodies (Figures 8.16–8.31). Serotonin (Paterson Dorsomedial Cell Column and Darnall, 2009) and nicotinic acetylcholine (Duncan The dorsomedial cell column (IODM) is best et al., 2008) receptor immunoreactivities and atrial natri- described as a dorsomedial satellite of IOA in the rostral uretic peptide (McKenzie et al., 2001) immunoreactive part of the latter (Figures 8.23–8.27). The IODM is small neurons have been detected in the human IOPr. and usually ovoid; it is depicted in the monkey by Bro- dal and Brodal (1981; in their figure 1) and in the cat by Marani et al. (1997, in their figure 4A). Conterminal Nucleus The conterminal nucleus (Ct) is located on the Ventrolateral Outgrowth lateral surface of the amiculum of the olive and The ventrolateral outgrowth (IOVL) is actually nuclei displays intense AChE reactivity in cell bodies and “g” and “h” of Olszewski and Baxter (1954) and of Braak neuropil (Figures 8.15–8.26). Filiano et al. (1990) identi- (1970). The alternative term is consistent with the nomen- fied that the ventrolateral neurons in the human con- clature now commonly used in studies with monkeys terminal nucleus are homologous to the neurons in (Bowman and Sladek, 1973; Brodal and Brodal, 1981), the cat chemosensitive area described by Trouth et al. cats (Marani et al., 1977), and rats (Paxinos and Watson, (1993). 2007). The ventrolateral out-growth is serpentine in the transverse plane, with its head (nucleus h) pointing dor- somedially (Figures 8.17, 8.18). It commences slightly Arcuate Nucleus more caudally than IODM and ends considerably short The arcuate nucleus (Ar) appears on the anterior of the rostral pole of IODM. It is parallel to the IOA and surface of the caudal hindbrain, extending dorsally at interposes itself between IOA and IOPr. the midline and partly surrounding the pyramid (Figures 8.19, 8.20). The Ar reacts densely for AChE, as Cap of Kooy do the pontine nuclei of which it is presumed to be a dis- The cap of Kooy (IOK) is present at the caudal pole of placed kin (Olszewski and Baxter, 1954; Mikhail and the olive and represents the most dorsal extension of the Ahmed, 1975). Sudden infant death syndrome is associ- complex at that level. It shows moderate AChE reac- ated with high-frequency hypoplasia, characterized by tivity (Figures 8.13–8.18). a volume reduction and neuronal depletion of Ar

III. BRAINSTEM AND CEREBELLUM 320 8. ORGANIZATION OF BRAINSTEM NUCLEI

(Filiano and Kinney, 1992; Matturri et al., 2002). Musca- hypoglossal nucleus, where it is succeeded by the pre- rinic cholinergic (Kinney et al., 1995), kainate (Panigrahy positus hypoglossal nucleus. The intercalated nucleus et al., 1997), and serotonergic receptors (Panigrahy et al., displays medium AChE reactivity, and some positive 2000) have been found deficient in the Ar of infants with cells can be detected through the neuropil. It starts as sudden infant death syndrome. Duncan et al. (2008) a narrow wedge between the 12N and the 10N but observed that 5-HT neurons as well as non-5-HT expands rostrally to fill the vacuum created by the neurons of the human Ar express a4 nicotinic acetylcho- lateral migration of the 10N (Figures 8.14–8.24). line receptors. This suggests that Ar is a site of Although In is characterized by small cells, at its rostral interaction where acetylcholine or influences pole a dense cluster of larger cells appears at the border the central response to . with 10N. These cells are probably the ones that react for Connections between the arcuate nucleus and the tyrosine hydroxylase (see Chapter 33). caudal raphe (including and nucleus raphe obscurus), superficial ventrolateral medullary regions (Zec et al., 1997) and the solitary Prepositus and Interpositus Nuclei nucleus (Zec and Kinney, 2003) have been shown in The prepositus nucleus (Pr) succeeds the intercalated human fetal . nucleus rostrally and displays a light AChE core sur- Angiotensin II type 1 (Benarroch et al., 1998), parathy- rounded by a region of greater reactivity (Figures 8.25– roid hormone 2 (Bago et al., 2009), and serotonergic 8.31). A distinct cluster of large cells well-stained for receptors (Paterson and Darnall, 2009), and adrenome- Nissl is found in the ventromedial tip of the Pr. The Pr dullin (Macchi et al., 2006) and glial cell line-derived is bordered medially by the oral dorsal paramedian neurotrophic factor (Quartu et al., 2007) immunoreactive and laterally by the interpositus nucleus (IPo) (Figures neurons have been observed in the human Ar. 8.26–8.30). Rostrally, Pr is succeeded by the AChE-dense region found immediately caudal and medial to the Paramedian and Dorsal Paramedian Nuclei abducens nucleus. This AChE-positive region may correspond to the pontine paramedian reticular nucleus Brodal and Gogstad’s (1957) paramedian groups involved in horizontal gaze. Dorsal to the 10N, Olszew- correspond to the clusters of AChE-positive cells and ski and Baxter outlined IPo to separate Pr from the neuropil seen within the predorsal bundle at the rostral medial vestibular nucleus. Dorsal and rostral to the pole of the hypoglossal nucleus. Olszewski and Baxter’s oral pole of Pr the supragenual nucleus can be detected dorsal paramedian groups resemble the pontine nuclei by medium AChE reactivity. in cytoarchitecture and AChE reactivity. The caudal Neurokinin (Covenas et al., 2003) and met-enkeph- dorsal paramedian nucleus (CDPMn) is distinguishable alin (Covenas et al., 2004) immunoreactivities have from the subjacent 12N, which is extremely AchE- been shown in the human Pr. reactive. The CDPMn is most prominent at the rostral pole of the 12N (Figures 8.26–8.29). The CDPMn is suc- ceeded rostrally by its oral companion (ODPMn). Cribriform Nucleus Studies in experimental animals suggest that cholinergic input to CDPMn is from the vestibular nuclei or prepos- The cribriform nucleus (Crb) was identified by Paxi- itus hypoglossal nucleus (Pr) (Barmack et al., 1992). nos and Huang (1995) as the area lateral to the solitary CDPMn is located adjacent and medial to the prepos- nucleus and medial to the dorsal column nuclei and itus nucleus in humans. In the mouse (Franklin and spinal vestibular nucleus. This area is generally AchE- Paxinos, 2008), rat (Paxinos and Watson, 2007), and rhe- positive while characteristically perforated by AChE- sus monkey (Paxinos et al., 2009) atlases, the region in negative fibers (Figures 8.21–8.25). which CDPMn is found is included in prepositus nucleus. This leads to the suggestion that CDPMn is involved in receiving vestibular input and participating Pontine Nuclei in the control of eye movements (Baizer et al., 2007). Cal- The pontine nuclei (Pn) attain their maximal relative retinin, parvalbumin, nitric oxide synthase, and SMI-32 size in the human, nearly throttling the dorsal pontine immunoreactivities have been shown in CDPMn (Baizer tegmentum. Their outposts are distinguishable by the et al., 2007). intense AChE reactivity of cell bodies and neuropil. As in other species, their main mass is found below the Intercalated Nucleus medial lemniscus. However, in the human, unlike the rat, there are pontine-like nuclei encircling and bisecting The intercalated nucleus (In) commences caudal to the rostral hindbrain. The pontobulbar nucleus (PnB) the obex and persists until the rostral pole of the lies outside the inferior cerebellar peduncle and appears

III. BRAINSTEM AND CEREBELLUM REFERENCES 321 caudally at the rostral pole of the external cuneate Cerebral Peduncle nucleus, presenting a triangular profile at this level (Figures 8.24, 8.25). At more rostral levels, the pontobul- We followed the nomenclature of Covenas et al. bar nucleus spreads to engulf this peduncle laterally and (2004) for naming the components of the cerebral ventrally. Further rostrally, it is broken up into large peduncle (cp), as corticospinal fibers (csp) and cortico- islands in the ventrolateral aspects of the medulla bulbar fibers (cbu) in our diagrams. (Figures 8.26–8.31). These islands are intermingled with the vestibular division of the vestibulocochlear nerve. The nuclei pararaphales (PaR) constitute two CONCLUSION paramedian chains of islands of pontine-like cells that bisect the medulla at rostral levels (Figure 8.29) (see This overview presents a classification of the human also Olszewski and Baxter, 1954). brainstem structures, including most of neuronal cell The reticular tegmental nucleus (RtTg) is located groups in the human brainstem. The most significant close to the midline above the medial lemniscus. It is conclusion of this overview is a glaring structural simi- found immediately rostral to the exiting sixth nerve larity of brainstem across species reflected by an impres- and it is replaced by MnR rostrally (Figures 8.35–8.45). sive number of homologies recognized between the RtTg consists of many clusters of cells usually brainstem of the human and that of other animals. While engulfed in AChE-reactive neuropil. Some cell clusters it can be hypothesized that there are human homologs to are associated with weak reactivity, though the cell nearly every nucleus identified in the rat brainstem, bodies are positive. The cells are distinguishable from species differences and even strain differences occur, those of the pontine nuclei because they are larger and and this compels us to establish homologies not by stain more intensely in Nissl preparations. extrapolation but by direct observation of human tissue. Functional mechanisms of the human brainstem, on Red Nucleus the other hand, remain hidden in connections, chemo- architecture, and physiology of neuronal groups. These The red nucleus is found at the level of the substantia characteristics are emerging from encouraging non- nigra as a sphere encapsulated within the ascending invasive imaging studies and expanding creative appli- superior cerebellar peduncle (Figures 8.55–8.64). At the cation of chemical analysis of the human brain. At that, level of the oculomotor nucleus, oculomotor nerve fibers a comparative structural plan of the brainstem funda- run along the surface of the red nucleus (Onodera and ment to interpret, convey, and compare these findings Hicks, 2009). is needed. In humans, the red nucleus consists of a magnocellu- lar part (RMC) and a parvicellular part (RPC). RMC neurons are found in a variety of sizes: giant, large, Acknowledgment medium, and small (Sobel, 1977). The number of giant- to-large-sized neurons is about 150–200 (Nathan and Supported by an NHMRC Australia Fellowship to G Paxinos (Grant #568605). The authors thank Reuben Png for construction of figures. Smith, 1982). In quadrupedal animals, such as the rat and cat, red nucleus consists mainly of the RMC (ten Donkelaar, 1988). References A large number of cells in the red nucleus are multi- polar and contain ferric iron pigment. These are Allien AM, McKinley MJ, Paxinos G, Oldfield BL, Mendelsohn EAO: assumed to be ectopically placed cells of the parabra- Angiotensin II receptors in the human nervous system. In Paxinos G, Mendelsohn EAO, editors: “Receptors in the Human chial pigmented nucleus, or of the caudal linear nucleus. Nervous System”, San Diego, 1991, Academic Press, pp 190–192. At rostral levels, the fasciculus retroflexus penetrates the Allien AM, Siew YC, Clevers J, McKinley ML, Paxinos G, red nucleus, separating a dorsomedial portion. The dor- Mendelsohn EAO: Localization and characterization of angio- somedial portion displays higher AChE reactivity. tensin II receptor binding and angiotensin converting enzyme in Immunohistochemical studies revealed the presence of the human , J Comp Neurol 269: 249-M4, 1988. Arango V, Ruggiero DA, Callaway JL, Anwar M, Reis DL, Mann JJ: parkin (Parkinson disease related protein) (Zarate- Catecholamine neurons in the ventrolateral medulla and nucleus Lagunes et al., 2001), somatostatin receptors (Selmer of the solitary tract in the human, J Comp Neurol 273:224–240, 1988. et al., 2000), as well as P2Y(1) purinergic receptor (Moore Austin MC, Rhodes JL, Lewis DA: Differential distribution of corti- et al., 2000) in the red nucleus of the human. The nucleus cotropin-releasing hormone immunoreactive axons in mono- is relatively large and current resolution of MRI and PET aminergic nuclei of the human brainstem, Neuropsychopharmacology 17:326–341, 1997. scans allows depiction of the red nucleus in the brain of Austin MC, Weikel JA, Arango V, Mann JJ: Localization of serotonin 5- the conscious human. For the connections of the red HT1A receptor mRNA in neurons of the human brainstem, nucleus, see Chapter 15. 18:276–279, 1994.

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