BrainBrain stemstem

MesencephalonMesencephalon ()(Midbrain) CNSCNS divisionsdivisions MidbrainMidbrain –– boundariesboundaries && sizesize

 CConnectsonnects thethe ponspons andand cerebellumcerebellum withwith thethe forebrainforebrain  TheThe smallestsmallest regionregion ofof thethe brainstembrainstem –– 66--7g7g  TheThe shortestshortest brainstembrainstem segmentsegment << 22 cmcm longlong BrainstemBrainstem divisionsdivisions

Midbrain Mesencephalon

Pons

Medulla Myelencephalon VentralVentral brainstembrainstem

cerebral peduncle

middle

pyramid VentralVentral midbrainmidbrain

Cranial Nerve 3

Cranial Nerve 4

Cerebral Peduncle DorsalDorsal brainbrain stemstem

Superior Cranial Nerve IV colliculus

Inferior colliculus

Middle cerebellar peduncle DorsalDorsal midbrainmidbrain

Brachium of the Brachium of the

Superior medullary velum Dorsal surface of the mesencephalon BrainBrain stemstem –– macroscopicmacroscopic overviewoverview

Dorsal view Ventral view

posterolateral sulcus median sulcus anterolateral sulcus OriginOrigin ofof CNSCNS subdivisionssubdivisions SecondarySecondary vesiclesvesicles MesencephalonMesencephalon isis largerlarger duringduring brainbrain developmentdevelopment thanthan inin postnatalpostnatal brainbrain

Neural tube folding (5 th -8th wk) AlarAlar vs.vs. BasalBasal plateplate derivativesderivatives -- ponspons

 somatic are alar plate Alar plate = afferent = sensory  visceral precursors migrated Basal plate = efferent = motor  visceral ventrally  somatic

The basal plate → primarily efferent nuclei (CN V, VI, VII, superior salivatory nuclei) The alar plate → somatic and visceral sensory nuclei (CN V, VIII, pontine nuclei) AlarAlar vs.vs. BasalBasal plateplate derivativesderivatives -- midbrainmidbrain Sensory Motor

visceral somatic 12 weeks

6 weeks

Neural canal

 Basal plate  motor nuclei of CN III & CN IV → extraocular muscles (somatic motor)  Edinger-Westphal nucleus → intraocular muscles (visceral motor)  Alar plate → tectum (colliculi)  Mixed basal & alar plate → , TThehe midbrainmidbrain hashas aa dorsoventraldorsoventral organization,organization, likelike thethe spinalspinal cord.cord.

ThisThis isis becausebecause thethe 44th ventricleventricle doesdoes notnot extendextend intointo thethe midbrainmidbrain ..

Spinal cord Midbrain

Neural canal

medulla AlarAlar vsvs basalbasal inin midbrainmidbrain

alar basal EstimatedEstimated timetime ofof developmentdevelopment ofof variousvarious brainbrain regiregionsons

2 mo 6 mo

Modified from Bayer SA et al. Neurotoxicology 14:83–144, 1993 LongitudinalLongitudinal zoneszones inin thethe brainbrain stemstem cranial

Structures in Midbrain:  Tectum ( =quadrigeminal plate) → superior & inferior colliculi +  → neuronal bodies + tracts passing  Basis = crus cerebri + substantia nigra ( “black substance ”)  neuronal axons – corticospinal/corticobulbar fibers  neuronal bodies – substantia nigra

caudal LongitudinalLongitudinal zoneszones inin thethe midbrainmidbrain cranial dorsal cerebral tectum aqueduct

tegmentum

basis

ventral caudal MesencephalicMesencephalic tectumtectum ((==quadrigeminalquadrigeminal plate)plate)

 SuperiorSuperior colliculicolliculi  InferiorInferior colliculicolliculi  CerebralCerebral aqueductaqueduct MidbrainMidbrain -- levellevel ofof superiorsuperior colliculuscolliculus

Superior Colliculus

Periaqueductal Gray

Cerebral Peduncles Red Nucleus ConnectionsConnections ofof superiorsuperior colliculuscolliculus

(visual)(visual) cortexcortex thalamusthalamus

eyeseyes superior colliculus cerebellumcerebellum

spinalspinal cordcord TectospinalTectospinal tracttract -- reflexive movement of head and neck ; eye movements

Origin: Superior Colliculus Course: Ventral to MLF, to ventromedial Termination: Cervical Spinal cord ventral horn Laterality: CONTRA (crosses immediately in the dorsal tegmental decussation)

The tectospinal tract carries impulses that control reflex movements of the upper trunk, neck, and eyes in response to visual stimuli.

Purves, et al, Neuroscience, 3rd ed. MidbrainMidbrain -- levellevel ofof inferiorinferior colliculuscolliculus

Inferior Colliculus

Periaqueductal Gray

Decussation of the Superior Cerebellar Peduncles

Cerebral Peduncles The nucleus of the inferior colliculus is a major relay nucleus in the auditory pathway Afferent connections Efferent connections Brachium of the Superior Colliculus Lateral Superior geniculate colliculus vision body

Brachium of the Inferior Colliculus Medial Inferior geniculate colliculus hearing body

The inferior colliculi are involved in auditory reflexes and in determining the side on which a sound originates MidbrainMidbrain colliculicolliculi && brachiabrachia

Brachium of the Superior Colliculus

Superior Brachium of the colliculus Inferior Colliculus Inferior colliculus CerebralCerebral aqueductaqueduct (Sylvius)(Sylvius)

~15 mm long contains no

3rd Ventricle 4th Ventricle

Obstruction of the cerebral aqueduct may occur congenitally, resulting in a non-communicating hydrocephalus. Pain control pathways & periaqueductal gray

cerebral aqueduct Ascending pain pathways StructuresStructures inin thethe mesencephalicmesencephalic tegmentumtegmentum

 CranialCranial nervenerve nucleinuclei –– CNCN III,III, IVIV  ReticularReticular formationformation -- nucleusnucleus locuslocus ceruleusceruleus && otherother  CrossingCrossing pathwayspathways  ascending (sensory)  superior cerebellar peduncle  lemniscal  spinothalamic  descending (motor)  central tegmental tract (basal ganglia /midbrain → inferior olive )   tectospinal tract  other – sympathetic fibers from hypothalamus; medial longitudinal fasciculus TheThe brainstembrainstem isis connectedconnected toto thethe cerebellumcerebellum viavia thethe cerebellarcerebellar pedunclespeduncles

superior cerebellar peduncle (SCP) Brachium conjunctivum MidbrainMidbrain ↔↔ CerebellumCerebellum SCP is the principal output path of the cerebellum

middle cerebellar peduncle (MCP) Brachium pontis PonsPons →→ CerebellumCerebellum

inferior cerebellar peduncle (MCP) MedullaMedulla oblongataoblongata ↔↔ CerebellumCerebellum The midbrain is connected with the cerebellum via SCP

SCP represents the main cerebellar SCP output to the thalamus and red nucleus

(ICP)

MCP MMajorajor ascendingascending andand descendingdescending tractstracts inin thethe mesencephalicmesencephalic tegmentumtegmentum

Lemniscal system CorticobulbarCorticobulbar tractstracts

MotorMotor inputinput to:to:  ReticularReticular formationformation –– mesencephalicmesencephalic  RedRed NucleusNucleus  CranialCranial NerveNerve motormotor nucleinuclei –– III,III, IVIV

Note – No direct connections from the primary motor cortex to III, IV, and VI; these nuclei get input from frontal and parietal cortex Cranial nerves – sensory nuclei Cranial nerves – motor nuclei CranialCranial nervenerve nucleinuclei inin brainbrain stemstem

Name Nerve Nuclei

Oculomotor III Oculomotor, Edinger–Westphal midbrain Trochlear IV Trochlear Trigeminal V Main sensory, spinal (descending), mesencephalic, motor (masticatory) Abducens VI Abducens Facial VII Facial, superior salivatory, gustatory (solitary)** Vestibulocochlear VIII Cochlear (2 nuclei), vestibular (4 nuclei) Glossopharyngeus IX Ambiguus*, inferior salivatory, solitary** Vagus X Dorsal motor, ambiguus**, solitary* medulla Accessory XI Spinal accessory (C1–5), ambiguus** Hypoglossal XII Hypoglossal

** The solitary nucleus is common for CN VII, IX, and X * The ambiguus nucleus is common for CN IX, X, and XI CNCN III:III: OculomotorOculomotor

Origin: (motor), Edinger-Westphal nucleus (Psym) Course: Interpeduncular Fossa, Cavernous Sinus, Sup Orb Fissure Termination: MR, SR, IR, IO; Levator Palpebrae, Constrictor Pupillae (Psym) Laterality: Ipsilateral to extraocular muscles; bilateral to parasympathetic ganglia CNCN III:III: OculomotorOculomotor

Edinger–Westphal

motor CNCN III:III: OculomotorOculomotor Motor Sensory somatic visceral visceral somatic

extraocular skeletal muscles MotorMotor innervationinnervation ofof thethe eyeeye

Striated (extraocular muscles) Striated (extraocular muscles) - innervation

CN IV CN VI

All other – CN III CNCN III:III: OculomotorOculomotor CNCN IV:IV: TrochlearTrochlear

Origin: Course: Quadrigeminal Cistern, Ambient Cistern, Cavernous Sinus, Sup Orb Fissure Termination: Superior oblique muscle Laterality: Contralateral CNCN IV:IV: TrochlearTrochlear

The nucleus is at the The nerve exits caudal to level of the SCP the inferior colliculus decussation Contralateral CNCN IV:IV: TrochlearTrochlear RedRed nucleusnucleus

 OOvoidvoid massmass ~~55 mmmm inin diameterdiameter  DDorsomedialorsomedial toto thethe substantiasubstantia nigranigra  PinkishPinkish inin freshfresh preparationspreparations →→ itsits neuronsneurons containcontain ironiron pigmentpigment CConnectionsonnections ofof thethe redred nucleusnucleus Afferent connections Efferent connections RubrospinalRubrospinal TractTract –– movementmovement ofof upperupper limbslimbs

Origin: Red nucleus Course: Dorsolateral with LCST in spinal cord Termination: Cervical Spinal cord ventral horn Laterality: CONTRA (crosses immediately in the ventral tegmental decussation) Rubrospinal tract The red nucleus receives cortical input; Rubrospinal fibers project on the same spinal cord laminae as does the → indirect corticospinal tract

Purves, et al, Neuroscience, 3rd ed. TheThe CNCN IIIIII motormotor fiberfiber passpass throughthrough thethe redred nucleusnucleus

Lesions of the red nucleus result in contralateral tremor StructuresStructures inin thethe mesencephalicmesencephalic basisbasis

 NeuronalNeuronal axonsaxons  CorticoCortico --pontoponto --cerebellarcerebellar fibersfibers  CorticospinalCorticospinal fibersfibers corticofugal fibers  CorticobulbarCorticobulbar fibersfibers  NeuronalNeuronal bodiesbodies -- SubstantiaSubstantia nigranigra CCorticospinalorticospinal andand corticobulbarcorticobulbar tractstracts CorticospinalCorticospinal tracttract

Origin: Primary motor cortex (BA 4) Course: Post Limb IC, Pyramids Termination: Spinal cord ventral horn Laterality: CONTRA (lateral), IPSI (anterior) Corticopontine tract

Origin: Premotor, primary motor, and primary somatosensory cortex Course: (A/P), cerebral peduncles, Pons Termination: Pontine nuclei Laterality: Ipsilateral Somatotopic organization of corticospinal & corticobulbar tracts SubstantiaSubstantia nigranigra (SN)(SN)

Pars compacta

Pars reticulata NeuronsNeurons inin SNSN

 ParsPars compactacompacta (SNpc)(SNpc) ––dorsal,dorsal, containingcontaining neuromelaninneuromelanin →→ dopaminedopamine  ParsPars reticulatareticulata (SNpr)(SNpr) –– ventral,ventral, ironiron compoundscompounds →→ Ach,Ach, GABA;GABA; SNprSNpr extendsextends rostrallyrostrally asas farfar asas thethe subthalamicsubthalamic region,region, andand isis consideredconsidered toto bebe homologoushomologous withwith thethe medialmedial segmentsegment ofof thethe globusglobus pallidus,pallidus, whichwhich itit resemblesresembles structurallystructurally TH staining of DAergic neurons in SN SubstantiaSubstantia nigranigra modulatesmodulates thethe loopsloops betweenbetween cortexcortex --basalbasal gangliaganglia

Cortex

(+)

Substantia (+) nigra Thalamus

(-)

Basal ganglia DamageDamage ofof SNpcSNpc neuronsneurons leadsleads toto ParkinsonParkinson ’’ss diseasedisease

Parkinson Normal

Lewy bodies in SNpc neuron, H&E Upper midbrain

Pars compacta

Pars reticulata LowerLower midbrainmidbrain

Pars compacta

Pars reticulata BloodBlood supplysupply ofof midbrainmidbrain

 Basilar artery → paramedian branch  oculomotor (III) nerve nucleus  red nucleus (RN)  Superior cerebellar artery → tectum  Posterior cerebral artery  basal branch → cerebral peduncle (CP)  dorsolateral branch → (ST), (ML), and SCP BloodBlood supplysupply ofof midbrainmidbrain –– clinicalclinical syndromessyndromes Inability to move the eyes up or down

Tremor + sensory deficiency

Hemiparesis + CN III paralysis