Introduction Lar Nucleus to the Dorsal Motor Nucleus of the Va Gus Nerve, the Nucleus of the Solitary Tract, and Some Brain Stem Medullary Sympathetic Regions

Home , Nucleus ambiguus, Solitary nucleus, Solitary tract, Vestibular nuclei

Journal of Vestibular Research, Vol. 7, No. 1, pp. 63-76, 1997 Copyright © 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 0957-4271/97 $17.00 + .00 ELSEVIER PIT S0957 -4271(96)00138-3

Original Contribution

CONNECTIONS BETWEEN THE VESTIBULAR NUCLEI AND BRAIN STEM REGIONS THAT MEDIATE AUTONOMIC FUNCTION IN THE RAT

Jennifer D. Porter and Carey D. Balaban

University of Pittsburgh, Department of Otolaryngology, Pittsburgh, Pennsylvania Reprint address: Jennifer D. Porter, PhD, University of Pittsburgh, Department of Otolaryngology, Eye and Ear Institute, 203 Lothrop St. Rm. 106A, Pittsburgh, PA 15213; Tel: (412) 647-8528; E-mail: [email protected]

D Abstract- Clinical observations have long in D Keywords- vestibular system; autonomic dicated a vestibular influence on autonomic func function; nucleus of the solitary tract; tion. Neuroanatomical studies in the rabbit and in parabrachial nucleus; rat. the cat have identified descending vestibulo-auto nomic pathways from the caudal portion of the medial vestibular nucleus and the inferior vestibu- Introduction lar nucleus to the dorsal motor nucleus of the va gus nerve, the nucleus of the solitary tract, and some brain stem medullary sympathetic regions. Previous experimental investigations of brain This study describes vestibulo-autonomic path stem circuitry responsible for vestibula-auto ways in rats. One group of Long-Evans rats re nomic interactions have focused on mecha ceived injections of tetramethylrhodamine dex nisms for vestibula-sympathetic reflexes. Natu tran into the caudal aspect of the vestibular ral vestibular stimulation elicits cardiovascular nuclear complex. Anterogradely labeled descend changes (1,2), and vestibular nerve lesions im ing fibers were traced bilaterally to lateral, vent pede compensation for orthostatic hypotension rolateral, and intermediate subnuclei of the nu (3). These reflexes are postulated to be medi cleus of the solitary tract and the dorsal motor ated by circuitry between the caudal medial ves nucleus of the vagus nerve. A small number of ax tibular nucleus (MVn), the inferior vestibular ons also projected bilaterally to the nucleus am nucleus (IVn), and the subretrofacial rostral biguus, the ventrolateral medulla, and the nucleus raphe magnus. Finally, anterogradely labeled as ventrolateral medulla (2,4,5). In addition to nat- cending fibers were traced from the caudal medial ural stimulation of the otolith organs, the per vestibular nucleus and the inferior vestibular nu ception of posture has been postulated to be reg cleus to the medial, lateral. ventrolateral. and Ko1- ulated by receptors in the trunk ( 6). It has been liker-Fuse regions of parabrachial nucleus. A sec proposed that perception of posture/verticality ond group of rats received iontophoretic injections involves integration of vestibular information of Fluoro-gold into the nucleus of the solitary tract to and visceral sensory information, specifically identify the cells of origin of the vestibulo-solitary visceral afferent information that reflects pool projection. Similar to findings in the rabbit (Bala ing of the blood in large blood vessels and pos ban and Beryozkin, 1994), retrogradely labeled sible renal graviceptors (6). cells were observed in the caudal medial vestibu Until recently, there had not been direct neu lar nucleus and the inferior vestibular nucleus. These findings are consistent with the hypothesis roanatomical evidence linking central vestibular that a common pattern of vestibular nuclear projec circuits to autonomic circuits in the brain stem. tions to autonomic regions is shared by rabbits, cats, Balaban and Beryozkin (7) provided the first evi and rats. Copyright© 1997 Elsevier Science Inc. dence of direct connections between the vestibu-

RECEIVED 1 July 1996; AccEPTED 16 September 1996. 63 64 J. D. Porter and C. D. Balaban lar nuclei and brain stem autonomic regions. to target an injection of Fluoro-gold (lj.LA, tip pos They identified connections between the caudal itive, 6 to 7 minutes) into the caudal half of NTS. aspect of the vestibular nuclear complex to the After the injection, the craniotomy was packed nucleus of the solitary tract (NTS) and the dor with Gelfoam and the incision line sutured. sal motor nucleus of the vagus nerve (DMX) (7), which are also present in the cat (8). More recently, Balaban (9) has described a more ex Anterograde and Retgrograde Tracing tensive system of vestibular nuclear projections to the parabrachial nucleus (PBN) and sympa After a survival time of 2 to 4 days, the rats thetic medullary regions. Since the vestibula were euthanized with a sodium pentobarbital autonomic pathways have been described pri overdose (1 00 mg/kg) and perfused transcar marily in the rabbit, it is unclear which of these dially with phosphate-buffered saline followed by pathways may be a common feature of mammals paraformaldehyde-lysine-sodium metaperiodate and which are species-specific. This study exam (PLP) fixative (7,9). The brains were then removed ined the potential neuroanatomical substrates for and cryoprotected in a 30% sucrose-50 mM the coordination of vestibula-autonomic interac phosphate buffer solution until they were sec tions in the rat. tioned. Frozen sections (40 ~m, coronal plane) were cut on a sliding microtome, and all sections were placed in 50 mM phosphate buffer (pH 7 .2 Materials and Methods to 7.4). Sections were mounted on subbed slides, dehydrated through a graded alcohol series, cleared Surgical Procedure in xylene, and coverslipped with nonfluorescent DPX. Labeled neurons, axons, and terminal end,. The procedures in these experiments were ings were visualized using a fluorescence micro approved by the University of Pittsburgh Insti scope. tutional Animal Care and Use Committee. Forty-one adult male Long-Evans rats weighing CHarting of injection sites and nomenclature for between 250 and 350 g were used in this study. vestibular nuclei, the parabrachial nucleus, and Twenty-five rats received injections of tetrame the nucleus of the solitary tract. The tetramethyl thylrhodamine dextran, and 16 received injec rhodamine injection sites were charted on a se tions ofFluoro-gold into MVn, IVn, X:Vn (vestib ries of standard coronal sections. The area of ef ular nucleus X), NTS, spinal trigeminal nucleus fective uptake was defined as the dense core and (Sp5), reticular formation, area postrema (AP), the surrounding halo region. The labeled axons hypoglossal nucleus (XII), and DMX. The rats were charted on a series of camera Iucida draw were anesthetized with sodium pentobarbital (25 ings taken from each subject. The sections dis mg!kg) and ketamine (7 .5 mg!kg). All surgical played were taken at variable intervals to permit procedures were carried out under NIH Guide an accurate representation of terminations within lines for the Care and Use of Laboratory Ani various nuclei and their subdivision. The interval mals. The head was fixed in a stereotaxic appara between successive sections for camera lucida tus (Narishige Instruments, Tokyo, Japan) with drawings averages between 280 and 320 ~m. the head tilted 45° nose-down. Skin and underly The nomenclature for the vestibular nuclei in the ing muscle layers were retracted to expose the rat distinguishes between the caudal aspect of the occipital bone, atlas, and atlanto-occipital mem medial vestibular nucleus (cMVn), the inferior brane. The medulla was exposed by removing vestibular nucleus (IVn), and XVn. The parabra the altanto-occipital membrane and enlarging the chial (PBN) and Kolliker-Fuse nucleus of the foramen magnum dorsally with rongeurs. Using pons is divided into the medial PBN, located the appropriate brain landmarks and stereotaxic ventromedial to to the superior cerebellar pend coordinates, a 26-gauge injection needle was used uncle and ventrolateral to the locus coeruleus to inject tetramethyl rhodamine dextran (10% so (LC), lateral PBN (LPBN) located dorsolateral lution, 100 nl). A glass micropipette was then used to the superior cerebellar peduncle (scp), and VN-Autonomic Projections 65 the ventrolateral PBN (VLPB) as well as the KF ICP: inferior cerebellar penduncle located ventrolateral to the scp (10). The KF cells int: intermediate subnucleus are larger, multipolar, and not densely packed. The IV n: inferior vestibular nucleus medial parabrachial nucleus is divided into small KF: Kolliker-Fuse nucleus spindle-shaped cells and medium multipolar (ex LPB: lateral parabrachial nucleus ternal division, MPBe) cells. The nucleus of the LC: locus coeruleus solitary tract (NTS) is divided into medial, in LVn: lateral vestibular nucleus termediate, ventral and ventrolateral, dorsal and Me5: mesencephalic 5 dorsal lateral, and interstitial subnuclei (11). MPB: medial parabrachial nucleus MPBe: external medial parabrachial nucleus List of Abbreviations MV n: medial vestibular nucleus amb: nucleus ambiguus cMVN: caudal aspect of medial vestibular nucleus DMX: dorsal motor nucleus of the vagus nerve MVnV: ventral aspect of medial vestibular nu- ECu: external cuneate cleus

23PVR 1BRFG 19RFG 23RFG 24PVR 11RFG 21RFG

Figure 1. Charting of tetramethyl rhodamine dextran injection sites into the caudal aspect of the vestibular nu clear complex. Eight injection sites are charted on a series of sections taken from a representative set of cam era Iucida drawings (sectioned at 40 1-Lm, every 280 to 320 1-Lm). Nucleus prepositus hypoglossi (prH}, nucleus tractus solitarius (NTS), and dorsal motor nucleus of the vagus nerve (DMX) are noted. These sections are ar ranged from caudal to rostral regions. 66 J. D. Porter and C. D. Balaban

NTS: nucleus tractus solitarius Anterogradely labeled fibers could be traced prH: nucleus prepositus hypoglossi in descending pathways to two regions: (1) NTS RM: nucleus raphe magnus and DMX, and (2) medullary sympathetic re RVL: rostral ventrolateral medulla gions. The vestibula-solitary fibers followed the s: solitary tract same trajectories that have been reported in the slt: lateral subnucleus rabbit (7) and cat (8). These axons descended in smd: medial subnucleus two fascicles, a lateral path and a medial path. spc: parvocellular subnucleus The lateral path fibers traveled caudally within sp5: nucleus of spinal 5 MVn before turning ventrally into NTS and Su VN: superior vestibular nucleus DMX (Figures 3A and 4). Other fibers followed svl: ventrolateral subnucleus the medial path to NTS, travelling caudally VLPB: ventrolateral parabrachial nucleus rhrough the nucleus prepositus hypoglossi to the XII: hypoglossal nucleus nucleus intercalatus (Figure 4 ). A few of these XV n: vestibular nucleus X fibers formed an axon plexus in the rostral as pect of nucleus intercalatus, while others pro ceeded caudally and laterally to terminate in the Results caudal half of the intermediate subnucleus of NTS. The densest terminations were observed Eight tetramethyl rhodamine dextran injec in the lateral, ventrolateral, and intermediate re tion sites were confined within the caudal por gions of NTS. Examples of anterogradely la tion of the medial vestibular nucleus and the in beled fibers in these regions are shown in Figure ferior vestibular nucleus without evidence of 3. The contralaterally projecting fibers emerged spread into the underlying rostral nucleus trac from the ventral border of the caudal medial tus solitarius, reticular formation, or medial lon vestibular nucleus, crossed the midline, and gitudinal fasciculus (Figure 1). Photomicro formed dense terminations in the contralateral graphs of representative injection sites are caudal medial and inferior vestibular nuclei. The shown in Figure 2, panels A and B. Any cases projections to NTS and DMX then followed the with evidence of spread into the reticular forma same course as the descending ipsilateral fibers. tion, NTS, or MLF were excluded from the Injections of the retrograde tracer Flouro-gold study because these areas also project to PBN into NTS were used to define the origin of these (12,13). No transport to autonomic regions was vestibule-solitary fibers. In 3 rats, injections of observed from control injections centered in the Fluoro-gold were centered within NTS were spinal trigeminal nucleus (sp5). The locations of spread into DMX, nucleus intercalatus, and the anterogradely labeled axons from the injections dorsal aspect of the hypoglossal nucleus. These sites in Figure 1 are summarized in Table 1. injections did not involve the nucleus prepositus

Table 1. Tetramethyl Rhodamine Dextran: A summary of rostral projections from caudal medial vestibular nucleus and inferior vestibular nucleus to nucleus of the solitary tract regions

Subject# Injection site SVL SLT SMD INT AMB VLM RM KF MPB MPBE LPB VLPB

18RFG MVn/IVn ++ ++ + + + + + + + ++ ++ ++ 19RFG IVn ++ ++ ++ + + + + + ++ 21RFG XVn/IVn ++ ++ + + + + + ++ ++ ++ 23RFG IVn ++ ++ + + + + + + + + 11RFG MVn/IVn ++ ++ + + + + + + + ++ +++ +++ 23PVR IVn ++ ++ + + + + + + + ++ + ++ 24PVR XVn/IVn ++ ++ + + ++ + ++ +++ +++ 27PVR MVn + ++ + ++ + + + +

Ventrolateral NTS (SVL), lateral NTS (SLT), medial NTS (SMD), and intermediate NTS (INT); medullary regions: nucleus ambig uus (AMB), ventrolateral medullary reticular formation (VLM), and nucleus raphe magnus (RM); parabrachial regions: Kolliker Fuse nucleus (KF), medial PBN (MPB), external MPB (MPBE), lateral PBN (LPB), ventrolateral PBN (VLPB). - = o axons; + = 1-5 axons; ++ = 6-10 axons; +++ = > 10 axons. VN-Autonomic Projections '67

Figure 2. Photomicrographs of tetramethyl rhodamine dextran sites injected into caudal regions of the vestibu lar nuclear complex and a flourogold site injected into caudal aspect of NTS. (A) This is an example of a tetram ethyl rhodamine dextran injection site involving the caudal aspect of IVn and MVn (case #18RFG). Antero gradely labeled axons involving the solitary nucleus produced by this injection are pictured in Figure 3, panels B-0. (B) This is another example of a tetramethyl rhodamine dextran injection site involving the caudal aspect of MVn and IVn (case 11 RFG). Anterogradely labeled axons resulting from this injection site are illustrated in Fig ure 4. (C) This is an example of a Fluoro-gold injection site involving NTS (28RGF). Retrogradely labeled cells resulting from this injection are shown in Figure 6 and their distribution illustrated in Figure 5. Scalebar: A & B 500 f.Lm, C 200 f.Lm. (j) ())

c._ 0 '"'0 0 ::::+ ~ PJ Figure 3. (A) This photograph shows the lateral path, a group of anterogradely labeled fibers resulting from the injection site pictured in Figure 2A, turning ventrally :::J Q.. into NTS. (B & C) These are examples of anterogradely labeled fibers in svl, resulting from the injection site pictured in 2A. (D) This anterogradely labeled fiber in sit 0 also resulted from the injection site pictured in 2A. The arrows show terminal endings and varicosities on the labeled fibers. Scalebar: 50 f!ITI. 0 OJ PJ i:i) o PJ :::J VN-Autonomic Projections 69

contralateral ipsilateral

svl r < I E B ·"91'\_ ~ /\\)~ c F ~

Figure 4. This illustration depicts the distribution of anterogradely labeled axons in the nucleus tractus solitar ius (NTS) from the injection site pictured in Figure 28 (case #11 RFG). The axons are charted on a series of cam era Iucida drawings of transverse sections through the medulla from a level immediately rostral to the obex through the caudal aspect of the commissural subnucleus of the solitary tract. s = solitary tract, DMX = dorsal motor nucleus of X, XII = hypoglossal nucleus, svl = ventrolateral subnucleus, sit = lateral subnucleus, int = intermediate subnucleus, smd = medial subnucleus, spc = parvocellular subnucleus. Note, the density of the terminations within the lateral and ventrolateral areas of NTS.

hypoglossi, the nucleus of RolleL or the medial of the vestibular nuclei. A few labeled cells longitudinal fasciculus. The site illustrated in were observed in the Kolliker Fuse nucleus and Figure 2C produced retrogradely labeled neu in the lateral parabrachial nucleus. rons bilaterally in the caudal aspect ofJ'viVn and Anterograde transport from tetramethyl IVn (Figures 5 and 6). The labeled neurons rhodamine dextran injections into MVn and IVn tended to occupy the ventral half of MVp and also revealed descending projections to brain IVn and appeared to be arranged in a line ex stem parasympathetic and sympathetic regions. tending from the medial to the lateral borders of Descending projections to the medullary teg the nuclei. The number of labeled cells in MVn mentum traveled caudally to innervate nucleus ranged from 16 to 29. The number of labeled ambiguus, ventrolateral medulla, and nucleus cells in IVn ranged from 12 to 36. There was no raphe magnus. Ipsilateral to the tetramethyl evidence of retrograde transport to other regions rhodamine dextran injection site, fibers excited 70 J. D. Porter and C. D. Balaban

contralateral

10RFG c=J 28RFG 0 7RFG tt

Figure 5. A series transverse sections taken from a standard series of sections throughout the vestibular nu clear complex. A few retrogradely labeled cells were observed throughout MVn and !Vn. These cells appeared to be equally distributed throughout the complex. ECu = external cuneate, X = vestibular nucleus X, MVn = me dial vestibular nucleus, MVnV = ventral aspect of the medial vestibular nucleus, IVn = inferior vestibular nu cleus, !CP = inferior cerebellar peduncle, PrH = prepositus hypoglossal nucleus, LVn = lateral vestibular nu cleus, SuVn = superior vestibular nucleus.

the ventral border of MVn and traversed the ros reticular formation (Figure 7). Other fibers tral NTS to center the dorsal aspect of the medul turned medially in the dorsal half of the reticu lary reticular formation. These fibers also trav lar formation, crossed the midline, and pro elled ventrally and laterally to form terminal jected ventrally to the contralateral nucleus am ramifications in the nucleus ambiguus, the lateral biguus, the lateral medullary reticular formation, medullary tegmentum, and the ventral medullary and the ventrolateral medulla. In addition, axons VN-Autonomic Projections

Figure 6. This photograph shows retrogradely labeled cells in MVn and IVn resulting from the Fluoro-gold in jection pictured in Figure 2C into NTS. (A) A pair of retrogradely labeled cells in cMVn. (B) Four retrogradely la beled multipolar cells in IVn. (C) 2 small triangular-shaped cells in cMVn. (D) A group of small and larger multi polar cells in IVn. Scalebar: 50 = J.Lm.

occasionally branched from the crossing fibers level of MV n and then followed the same course on either side of the midline and descended ven as the ipsilateral fibers. These axons formed vari trally to innervate the nucleus raphe magnus. cosities and terminal bouton-like processes near Ascending projections from caudal regions cell bodies in these regions of the parabrachial of MVn and IVn to PBN followed the same complex (Figure 9). The densest terminations path as described in the rabbit (9). Antero were centered bilaterally in the ventrolateral as gradely labeled axons emerged from the injec pect of the Kolliker -Fuse nucleus and in the lat tion sites and traveled rostrally and laterally in eral and ventrolateral parabrachia1 nuclei. The MVN to enter the most lateral and ventral as distribution tc MPB and 1\1?Be was sparser. with pect of LVn. These fibers continued rostrally in fibers located in more caudal and ventral regions the ventral half of LV n, entered the ventrolat of these areas, where vmicose axons traversed eral margin of SVn, and then turned dorsally to cell bodies. Figure 8 illustrates the distribution of innervate caudal regions of MPB and LPB. the terminations within PBN on a series of trans Other fibers continued rostrally and medially to verse sections. innervate the locus coeruleus, the external divi sion of the medial parabrachial nucleus, the ventral division of the lateral parabrachial nu Discussion cleus, and the ventrolateral aspect of the Kol liker-Fuse nucleus (Figure 8). The contralateral The pattern of vestibular nucleus projections axons that projected from the caudal aspect of in the rat is consistent with the hypothesis that MVn and IVn to PBN crossed midline at the there is a common set of vestibula-autonomic 72 J. D. Porter and C. D. Balaban

contralateral ipsilateral

Figure 7. This illustration depicts the distribution of anterogradely labeled axons in medullary regions resulting from the injection site pictured in Figure 28 (case #11RFG). The sections are displayed from rostral to caudal regions, throughout the level of nucleus ambiguus (amb), nucleus raphe magnus (RM), and rostral ventrolateral medulla (RVL). The nucleus of spinal 5 is noted (sp5), and the lateral reticular nucleus is 160 f.tm caudal to section 5. VN-Autonomic Projections 73

contralateral ipsilateral

VLPB VLPE

Figure 8. This illustration depicts the distribution of anterogradely labeled axons in parabrachial nucleus result· ing from the injection site pictured in Figure 2A (case 18RFG). Axons are charted on a series of traverse sec tions throughout the Kolliker-fuse nucleus (KF), lateral PBN (LPB), medial PBN (MPB), external MPB (MPBe), and ventrolateral PBN (VLPB). Locus coeruleus (LC) and mesencephalic 5 (Me5) are noted. pathways in at least rodents and lagomorphs. fined to the lateral, ventrolateral, and intermedi The fiber pathways and terminal regions of ves ate subnuclei of NTS. Since the dorsal respira tibular nucleus projections to the nucleus tractus tory group includes the ventrolateral subnucleus solitarius, the dorsal motor nucleus of the vagus of NTS (14), this pathway may contribute to nerve, the ventrolateral medulla, the nucleus respiratory responses to vestibular stimulation ambiguus, the nucleus raphe magnus, and the in these species (15). By contrast, the cat has parabrachial complex in pigmented rats are relatively dense projections to the medial sub strikingly similar to observations in albino rab nucleus of NTS and a paucity of terminations in bits. (7 ,9). The similarity in the organization of the ventrolateral subnucleus. Since the medial vestibula-solitary projections in rats, rabbits (7), subnucleus of NTS receives dense gastrointesti and cats (8) further suggests that mammals may nal input (12,13,16), this pathway may contrib share a common pattern of vestibular nucleus con ute to increased salivation, retching, and emesis nections with autonomic brain stem structures. during motion sickness and vestibular dysfunc Despite the interspecies similarity between tion in this species. The lack of a convincing vestibula-solitary pathways, there appear to be projection to the dorsal respiratory group region subtle species differences in the relative distri in the cat is also consistent with the report that bution of terminals in the nucleus tractus soli dorsal respiratory group lesions in cats do not tarius. The subnuclear distribution of vestibula affect vestibulo-respiratory responses (17). solitary terminations is indistinguishable in rats The subnuclear distribution of vestibulo and rabbits (7), with densest terminations con- parabrachial projections in rats is generally similar 74 J. D. Porter and C. D. Balaban

Figure 9. These are a series of photomicrographs of terminations in PBN resulting from the injection site pic tured in Figure 2A (case 18RFG). Anterogradely labeled axons often displayed varicosities and terminal bouton like endings, shown by the arrows. Scalebar: 50 J.tm. VN-Autonomic Projections 7.5 to the pattern in rabbits. Both species display pairing a novel taste with chemical stimuli that projections to the caudal aspect of the medial elicit gastrointestinal malaise) in rats is im parabrachial nucleus, the ventrolateral aspect of paired specifically by ablation of the gustatory the Kolliker-Fuse nucleus, and the external me regions of the parabrachial nucleus (26). These dial parabrachial nucleus (9). However, the den findings raise the hypothesis that a similar inte sity of projections to the lateral and the ventro gration of gustatory, gastrointestinal, and vesti lateral parabrachial nucleus are considerably bular input in the medial parabrachial nucleus more prominent in rats. These regions of the lat will be essential for the development of motion eral parabrachial nucleus receive ascending in induced conditioned taste aversion. This direct put from the medial subnucleus of NTS and the convergence may account for the resemblance area postrema (18) and descending input from between motion sickness and responses to in cerebral cortex and the amygdala (19); they gestion of toxins (27). send projections to the hypothalamus (20). The existence of a network of vestibular nu Hence, these connections may suggest a greater clear connections with central autonomic path contribution of vestibular input to neuroendo ways suggests that vestibular nucleus outputs crine responses in rats than in rabbits. are an integral part of signal processing in both The convergence of vestibular and gustatory descending and ascending autonomic pathways. information in the medial parabrachial nucleus The descending vestibular nuclear projections may serve as an neural substrate for the devel to the solitary nucleus and the sympathetic and opment of motion-induced conditioned taste parasympathetic brain stem regions are likely to aversions, which are a hallmark of motion sick contribute to the effects of vestibular ·stimula ness in rats (21). Vestibular projections to the tion on cardiovascular and respiratory control medial parabrachial nucleus include regions (2,28). However, there is recent evidence that that receive ascending gustatory inputs from the both vestibular and visceral signals contribute to rostral aspect of the nucleus of the solitary tract perception of the spatial vertical (6) and that a (18,22) and that respond to gustatory and orofa common pattern of space and motion discomfort cial stimuli (23,24). The caudal aspect of the is reported by patients with vestibular dysfunc medial parabrachial nucleus also receives gas tion, panic disorder with agoraphobia, agorapho trointestinal afferent information via a relay in bia without panic, and height phobias (29). Since the medial subnucleus of the nucleus of the soli the parabrachial nucleus is connected recipro tary tract (16,18,25). The importance of this cally with the hypothalfuuus, prefrontal cortex, convergence of visceral and gustatory inputs is and amygdala, these vestibulo-parabrachial pro indicated by the demonstration that the acquisi jections provide a potential neural substrate for tion of conditioned taste aversions (elicited by perceptual and affective phenomena.

REFERENCES

1. Yates BJ. Miller AD. Properties of sympathetic reflexes 7. Balaban CD. Beryozkin G. Vestibular nucleus projections elicited by natural vestibular stimulation: implications for to nucleus tractus solitarius and the dorsal motor nucleus cardiovascular control. J Neurophysiol J 994;71 :2087-92. of the vagus nerve: potential substrates for vestibula 2. Yates BJ. Vestibular influences on cardiovascular con autonomic interactions. Exp Brain Res 1994;98:200-12. trol. In Yates BJ, Miller AD, eds. Vestibular automonic 8. Yates BJ, Grelot L, Kerman IA, Balaban CD, Jakus J, regulation. CRC Press; 1996:97-111. Miller AD. The organization of vestibular inputs to 3. Doba N, Reis DJ. Role of the cerebellum and vestibular nucleus tractus solitarius (NTS) and adjacent structures in apparatus in regulation of orthostatic reflexes in the cat. the cat brainstem. Am J Physiol 1994;267:R974-R983. Cir Res 1974;34:9-18. 9. Balban CD. Vestibular nucleus projections to the 4. Uchino Y, Kudo N, Tsuda K, Iwamura Y. Vestibular parabrachial nucleus in rabbits; implications for vestib inhibition of sympathetic nerve activities. Brain Res ular influences on autonomic function. Exp Brain Res 1970;22: 195-206. 1996; 108:367-81. 5. Yates B, Yamagata Y, Bolton P. The ventrolateral 10. Saper C, Loewy A. Efferent connections of the parabra medulla of the cat mediates vestibula-sympathetic chial nucleus in the rat. Brain Res 1980; 197:291-317. reflexes. Brain Res 1991;552:265-272. 11. Kalia M, Sullivan M. Brain stem projections of sensory 6. Mittelstaedt H. Somatic graviception. Biol Psychol and motor components of the vagus nerve in the rat. J 1996;42:53-74. Comp Neurol1982;211:248-64. 76 J.D.Porterand C.D.B~aban

12. Norgren R. Projections from the nucleus of the solitary the magnitude of body rotation-induced conditioned tract in the rat. Neurosci 1978;3:207-18. taste aversions. Behav Neural Biol1983;38:82-96. 13. Shapiro RE, Miselis RR. The central organization of 22. Norgren R, Pfaffman C. The pontine taste area in the the vagus nerve innervating the stomach of the rat. J rat. Brain Res 197 5 ;91 :99-117. Comp Neurol1985;238:473-88. 23. DiLorenzo PM, Schwartzbaum JS. Coding of gustatory 14. Cohen MI. Central determinants of respiratory rhythms. information in the pontine parabrachial nuclei of the Annu Rev Phsyiol 1981 ;43:91-104. rabbit: magnitude of the neural response. Brain Res 15. Spiegel EA, Sommer I. Vestibular mechanisms. In: 1982;251 :229-44. Glasser 0, ed. Medical physics. Chicago: Year Book 24. DiLorenzo PM, Schwartzbaum JS. Coding of gustatory Publishers; 1994:1638-55. information in the pontine parabrachial nuclei of the 16. Leslie RA, Gwyn DO, Hopkins DA. The central distri rabbit: temporal patterns of neural response. Brain Res bution of the cervical vagus nerve and gastric afferent 1982251:245-57. and efferent projections in the rat. Brain Res Bull 25. Kalia M, Mesulam M. Brain stem projections of sensory 1982;8:37-43. and motor components of the vagus complex in the cat: 2, 17. Yates BJ, Siniaia MS, Miller AD. Descending path Laryngeal, tracheobronchial, pulmonary, cardiac and gas ways necessary for vestibular int1uences on sympa trointestinal branches. J Comp Neuroll980;193:467-508. thetic and inspiratory outflow. Am J Physiol 1995;268: 26. Spector AC, Norgren R, Grill H. Parabrachial gustatory R1381-Rl385. lesions impair taste aversion learning in rats. Behav 18. Herbert H, Moga MM, Saper CB. Connections of the Neurosci 1992;106: 147-61. parabrachial nucleus with the nucleus of the solitary 27. Money KE, Lackner JR, Cheung SK. The autonomic tract and the medullary reticular formation in the rat. J system and motion sickness. In: Yates BJ, Miller AD, Comp Neurol1990;293:540-80. eds. Vestibular autonomic regulation. CRC Press; 19. Moga MM, Herbert H, Hurley KM, Yasui Y, Gray TS, 1996:147-73. Saper CB. Organization of cortical, basal forebrain and 28. Miller AD, Yates BJ. Vestibular effects on respiratory hypothalamic afferents to the parabrachial nucleus in activity. In: Yates BJ, Miller AD, eds. Vestibular auto the rat. J Comp Neurol1990;295:624-61. nomic regulation, CRC Press; 1996:113-25. 20. Fulweiler CE, Saper CB. Subnuclear organization of 29. Jacob RJ, Furman JM, Perel JM. Panic, phobia and ves the efferent connections of the parabrachial nucleus in tibular dysfunction. In: Yates BJ, Miller AD, eds. Ves the rat. Brain Res Rev 1984;7:229-59. tibular autonomic regulation, CRC Press; 1996:197- 21. Ossenkopp KP. Area postrema lesions in rats enhance 227.