Journal of Vestibular Research, Vol. 7, No. 1, pp. 63-76, 1997 Copyright © 1997 Elsevier Science Inc. Printed in the USA. All rights reserved

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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: jdporter@pitt.edu

D Abstract- Clinical observations have long in­dicated a vestibular influence on autonomic func­tion. Neuroanatomical studies in the rabbit and in the cat have identified descending vestibulo-auto­nomic pathways from the caudal portion of the medial vestibular nucleus and the inferior vestibu-lar nucleus to the dorsal motor nucleus of the va­gus nerve, the nucleus of the solitary tract, and some brain stem medullary sympathetic regions. This study describes vestibulo-autonomic path­ways in rats. One group of Long-Evans rats re­ceived injections of tetramethylrhodamine dex­tran into the caudal aspect of the vestibular nuclear complex. Anterogradely labeled descend­ing fibers were traced bilaterally to lateral, vent­rolateral, and intermediate subnuclei of the nu­cleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. A small number of ax­ons also projected bilaterally to the nucleus am­biguus, the ventrolateral medulla, and the nucleus raphe magnus. Finally, anterogradely labeled as­cending fibers were traced from the caudal medial vestibular nucleus and the inferior vestibular nu­cleus to the medial, lateral. ventrolateral. and Ko1-liker-Fuse regions of parabrachial nucleus. A sec­ond group of rats received iontophoretic injections of Fluoro-gold into the nucleus of the solitary tract to identify the cells of origin of the vestibulo-solitary projection. Similar to findings in the rabbit (Bala­ban and Beryozkin, 1994), retrogradely labeled cells were observed in the caudal medial vestibu­lar nucleus and the inferior vestibular nucleus. These findings are consistent with the hypothesis that a common pattern of vestibular nuclear projec­tions to autonomic regions is shared by rabbits, cats, and rats. Copyright© 1997 Elsevier Science Inc.

D Keywords- vestibular system; autonomic function; nucleus of the solitary tract; parabrachial nucleus; rat.

Introduction

Previous experimental investigations of brain stem circuitry responsible for vestibula-auto­nomic interactions have focused on mecha­nisms for vestibula-sympathetic reflexes. Natu­ral vestibular stimulation elicits cardiovascular changes (1,2), and vestibular nerve lesions im­pede compensation for orthostatic hypotension (3). These reflexes are postulated to be medi­ated by circuitry between the caudal medial ves­tibular nucleus (MVn), the inferior vestibular nucleus (IVn), and the subretrofacial rostral ventrolateral medulla (2,4,5). In addition to nat-ural stimulation of the otolith organs, the per­ception of posture has been postulated to be reg­ulated by receptors in the trunk ( 6). It has been proposed that perception of posture/verticality involves integration of vestibular information and visceral sensory information, specifically visceral afferent information that reflects pool­ing of the blood in large blood vessels and pos­sible renal graviceptors (6).

Until recently, there had not been direct neu­roanatomical evidence linking central vestibular circuits to autonomic circuits in the brain stem. Balaban and Beryozkin (7) provided the first evi­dence of direct connections between the vestibu-

RECEIVED 1 July 1996; AccEPTED 16 September 1996.

63

64

lar nuclei and brain stem autonomic regions. They identified connections between the caudal aspect of the vestibular nuclear complex to the nucleus of the solitary tract (NTS) and the dor­sal motor nucleus of the vagus nerve (DMX) (7), which are also present in the cat (8). More recently, Balaban (9) has described a more ex­tensive system of vestibular nuclear projections to the parabrachial nucleus (PBN) and sympa­thetic medullary regions. Since the vestibula­autonomic pathways have been described pri­marily in the rabbit, it is unclear which of these pathways may be a common feature of mammals and which are species-specific. This study exam­ined the potential neuroanatomical substrates for the coordination of vestibula-autonomic interac­tions in the rat.

Materials and Methods

Surgical Procedure

The procedures in these experiments were approved by the University of Pittsburgh Insti­tutional Animal Care and Use Committee. Forty-one adult male Long-Evans rats weighing between 250 and 350 g were used in this study. Twenty-five rats received injections of tetrame­thylrhodamine dextran, and 16 received injec­tions ofFluoro-gold into MVn, IVn, X:Vn (vestib­ular nucleus X), NTS, spinal trigeminal nucleus (Sp5), reticular formation, area postrema (AP), hypoglossal nucleus (XII), and DMX. The rats were anesthetized with sodium pentobarbital (25 mg!kg) and ketamine (7 .5 mg!kg). All surgical procedures were carried out under NIH Guide­lines for the Care and Use of Laboratory Ani­mals. The head was fixed in a stereotaxic appara­tus (Narishige Instruments, Tokyo, Japan) with the head tilted 45° nose-down. Skin and underly­ing muscle layers were retracted to expose the occipital bone, atlas, and atlanto-occipital mem­brane. The medulla was exposed by removing the altanto-occipital membrane and enlarging the foramen magnum dorsally with rongeurs. Using the appropriate brain landmarks and stereotaxic coordinates, a 26-gauge injection needle was used to inject tetramethyl rhodamine dextran (10% so­lution, 100 nl). A glass micropipette was then used

J. D. Porter and C. D. Balaban

to target an injection of Fluoro-gold (lj.LA, tip pos­itive, 6 to 7 minutes) into the caudal half of NTS. After the injection, the craniotomy was packed with Gelfoam and the incision line sutured.

Anterograde and Retgrograde Tracing

After a survival time of 2 to 4 days, the rats were euthanized with a sodium pentobarbital overdose (1 00 mg/kg) and perfused transcar­dially with phosphate-buffered saline followed by paraformaldehyde-lysine-sodium metaperiodate (PLP) fixative (7,9). The brains were then removed and cryoprotected in a 30% sucrose-50 mM phosphate buffer solution until they were sec­tioned. 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 to 7.4). Sections were mounted on subbed slides, dehydrated through a graded alcohol series, cleared in xylene, and coverslipped with nonfluorescent DPX. Labeled neurons, axons, and terminal end,. ings were visualized using a fluorescence micro­scope.

CHarting of injection sites and nomenclature for vestibular nuclei, the parabrachial nucleus, and the nucleus of the solitary tract. The tetramethyl rhodamine injection sites were charted on a se­ries of standard coronal sections. The area of ef­fective uptake was defined as the dense core and the surrounding halo region. The labeled axons were charted on a series of camera Iucida draw­ings taken from each subject. The sections dis­played were taken at variable intervals to permit an accurate representation of terminations within various nuclei and their subdivision. The interval between successive sections for camera lucida drawings averages between 280 and 320 ~m. The nomenclature for the vestibular nuclei in the rat distinguishes between the caudal aspect of the medial vestibular nucleus ( cMVn), the inferior vestibular nucleus (IVn), and XVn. The parabra­chial (PBN) and Kolliker-Fuse nucleus of the pons is divided into the medial PBN, located ventromedial to to the superior cerebellar pend­uncle and ventrolateral to the locus coeruleus (LC), lateral PBN (LPBN) located dorsolateral to the superior cerebellar peduncle (scp), and

VN-Autonomic Projections

the ventrolateral PBN (VLPB) as well as the KF located ventrolateral to the scp (10). The KF cells are larger, multipolar, and not densely packed. The medial parabrachial nucleus is divided into small spindle-shaped cells and medium multipolar (ex­ternal division, MPBe) cells. The nucleus of the solitary tract (NTS) is divided into medial, in­termediate, ventral and ventrolateral, dorsal and dorsal lateral, and interstitial subnuclei (11).

List of Abbreviations amb: nucleus ambiguus DMX: dorsal motor nucleus of the vagus nerve ECu: external cuneate

23PVR

1BRFG

19RFG

23RFG

24PVR

11RFG

21RFG

ICP: inferior cerebellar penduncle int: intermediate subnucleus IV n: inferior vestibular nucleus KF: Kolliker-Fuse nucleus LPB: lateral parabrachial nucleus LC: locus coeruleus LVn: lateral vestibular nucleus Me5: mesencephalic 5 MPB: medial parabrachial nucleus MPBe: external medial parabrachial nucleus MV n: medial vestibular nucleus

65

cMVN: caudal aspect of medial vestibular nucleus MVnV: ventral aspect of medial vestibular nu-

cleus

Figure 1. Charting of tetramethyl rhodamine dextran injection sites into the caudal aspect of the vestibular nu­clear complex. Eight injection sites are charted on a series of sections taken from a representative set of cam­era 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 ar­ranged from caudal to rostral regions.

66

NTS: nucleus tractus solitarius prH: nucleus prepositus hypoglossi RM: nucleus raphe magnus RVL: rostral ventrolateral medulla s: solitary tract slt: lateral subnucleus smd: medial subnucleus spc: parvocellular subnucleus sp5: nucleus of spinal 5 Su VN: superior vestibular nucleus svl: ventrolateral subnucleus VLPB: ventrolateral parabrachial nucleus XII: hypoglossal nucleus XV n: vestibular nucleus X

Results

Eight tetramethyl rhodamine dextran injec­tion sites were confined within the caudal por­tion of the medial vestibular nucleus and the in­ferior vestibular nucleus without evidence of spread into the underlying rostral nucleus trac­tus solitarius, reticular formation, or medial lon­gitudinal fasciculus (Figure 1). Photomicro­graphs of representative injection sites are shown in Figure 2, panels A and B. Any cases with evidence of spread into the reticular forma­tion, NTS, or MLF were excluded from the study because these areas also project to PBN (12,13). No transport to autonomic regions was observed from control injections centered in the spinal trigeminal nucleus (sp5). The locations of anterogradely labeled axons from the injections sites in Figure 1 are summarized in Table 1.

J. D. Porter and C. D. Balaban

Anterogradely labeled fibers could be traced in descending pathways to two regions: (1) NTS and DMX, and (2) medullary sympathetic re­gions. The vestibula-solitary fibers followed the same trajectories that have been reported in the rabbit (7) and cat (8). These axons descended in two fascicles, a lateral path and a medial path. The lateral path fibers traveled caudally within MVn before turning ventrally into NTS and DMX (Figures 3A and 4). Other fibers followed the medial path to NTS, travelling caudally rhrough the nucleus prepositus hypoglossi to the nucleus intercalatus (Figure 4 ). A few of these fibers formed an axon plexus in the rostral as­pect of nucleus intercalatus, while others pro­ceeded caudally and laterally to terminate in the caudal half of the intermediate subnucleus of NTS. The densest terminations were observed in the lateral, ventrolateral, and intermediate re­gions of NTS. Examples of anterogradely la­beled fibers in these regions are shown in Figure 3. The contralaterally projecting fibers emerged from the ventral border of the caudal medial vestibular nucleus, crossed the midline, and formed dense terminations in the contralateral caudal medial and inferior vestibular nuclei. The projections to NTS and DMX then followed the same course as the descending ipsilateral fibers.

Injections of the retrograde tracer Flouro-gold into NTS were used to define the origin of these vestibule-solitary fibers. In 3 rats, injections of Fluoro-gold were centered within NTS were spread into DMX, nucleus intercalatus, and the dorsal aspect of the hypoglossal nucleus. These 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 ambig­uus (AMB), ventrolateral medullary reticular formation (VLM), and nucleus raphe magnus (RM); parabrachial regions: Kolliker­Fuse 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 vestibu­lar nuclear complex and a flourogold site injected into caudal aspect of NTS. (A) This is an example of a tetram­ethyl rhodamine dextran injection site involving the caudal aspect of IVn and MVn (case #18RFG). Antero­gradely 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 Fig­ure 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.

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 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 also resulted from the injection site pictured in 2A. The arrows show terminal endings and varicosities on the labeled fibers. Scalebar: 50 f!ITI.

(j) ())

c._

0

'"'0 0 ::::+ ~ PJ :::J Q..

0

0 OJ PJ i:i) o­PJ :::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 solitar­ius (NTS) from the injection site pictured in Figure 28 (case #11 RFG). The axons are charted on a series of cam­era 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 longitudinal fasciculus. The site illustrated in Figure 2C produced retrogradely labeled neu­rons bilaterally in the caudal aspect ofJ'viVn and IVn (Figures 5 and 6). The labeled neurons tended to occupy the ventral half of MVp and IV n and appeared to be arranged in a line ex­tending from the medial to the lateral borders of the nuclei. The number of labeled cells in MV n ranged from 16 to 29. The number of labeled cells in IVn ranged from 12 to 36. There was no evidence of retrograde transport to other regions

of the vestibular nuclei. A few labeled cells were observed in the Kolliker Fuse nucleus and in the lateral parabrachial nucleus.

Anterograde transport from tetramethyl rhodamine dextran injections into MVn and IVn also revealed descending projections to brain stem parasympathetic and sympathetic regions. Descending projections to the medullary teg­mentum traveled caudally to innervate nucleus ambiguus, ventrolateral medulla, and nucleus raphe magnus. Ipsilateral to the tetramethyl 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 nu­clear 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 = me­dial vestibular nucleus, MVnV = ventral aspect of the medial vestibular nucleus, IVn = inferior vestibular nu­cleus, !CP = inferior cerebellar peduncle, PrH = prepositus hypoglossal nucleus, LVn = lateral vestibular nu­cleus, SuVn = superior vestibular nucleus.

the ventral border of MVn and traversed the ros­tral NTS to center the dorsal aspect of the medul­lary reticular formation. These fibers also trav­elled ventrally and laterally to form terminal ramifications in the nucleus ambiguus, the lateral medullary tegmentum, and the ventral medullary

reticular formation (Figure 7). Other fibers turned medially in the dorsal half of the reticu­lar formation, crossed the midline, and pro­jected ventrally to the contralateral nucleus am­biguus, the lateral medullary reticular formation, 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 in­jection pictured in Figure 2C into NTS. (A) A pair of retrogradely labeled cells in cMVn. (B) Four retrogradely la­beled multipolar cells in IVn. (C) 2 small triangular-shaped cells in cMVn. (D) A group of small and larger multi­polar cells in IVn. Scalebar: 50 = J.Lm.

occasionally branched from the crossing fibers on either side of the midline and descended ven­trally to innervate the nucleus raphe magnus.

Ascending projections from caudal regions of MVn and IVn to PBN followed the same path as described in the rabbit (9). Antero­gradely labeled axons emerged from the injec­tion sites and traveled rostrally and laterally in MVN to enter the most lateral and ventral as­pect of LVn. These fibers continued rostrally in the ventral half of LV n, entered the ventrolat­eral margin of SVn, and then turned dorsally to innervate caudal regions of MPB and LPB. Other fibers continued rostrally and medially to innervate the locus coeruleus, the external divi­sion of the medial parabrachial nucleus, the ventral division of the lateral parabrachial nu­cleus, and the ventrolateral aspect of the Kol­liker-Fuse nucleus (Figure 8). The contralateral axons that projected from the caudal aspect of MVn and IVn to PBN crossed midline at the

level of MV n and then followed the same course as the ipsilateral fibers. These axons formed vari­cosities and terminal bouton-like processes near cell bodies in these regions of the parabrachial complex (Figure 9). The densest terminations were centered bilaterally in the ventrolateral as­pect of the Kolliker -Fuse nucleus and in the lat­eral and ventrolateral parabrachia1 nuclei. The distribution tc MPB and 1\1?Be was sparser. with fibers located in more caudal and ventral regions of these areas, where vmicose axons traversed cell bodies. Figure 8 illustrates the distribution of the terminations within PBN on a series of trans­verse sections.

Discussion

The pattern of vestibular nucleus projections in the rat is consistent with the hypothesis that 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

3

a 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 sec­tions 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. The fiber pathways and terminal regions of ves­tibular nucleus projections to the nucleus tractus solitarius, the dorsal motor nucleus of the vagus nerve, the ventrolateral medulla, the nucleus ambiguus, the nucleus raphe magnus, and the parabrachial complex in pigmented rats are strikingly similar to observations in albino rab­bits. (7 ,9). The similarity in the organization of vestibula-solitary projections in rats, rabbits (7), and cats (8) further suggests that mammals may share a common pattern of vestibular nucleus con­nections with autonomic brain stem structures.

Despite the interspecies similarity between vestibula-solitary pathways, there appear to be subtle species differences in the relative distri­bution of terminals in the nucleus tractus soli­tarius. The subnuclear distribution of vestibula­solitary terminations is indistinguishable in rats and rabbits (7), with densest terminations con-

fined to the lateral, ventrolateral, and intermedi­ate subnuclei of NTS. Since the dorsal respira­tory group includes the ventrolateral subnucleus of NTS (14), this pathway may contribute to respiratory responses to vestibular stimulation in these species (15). By contrast, the cat has relatively dense projections to the medial sub­nucleus of NTS and a paucity of terminations in the ventrolateral subnucleus. Since the medial subnucleus of NTS receives dense gastrointesti­nal input (12,13,16), this pathway may contrib­ute to increased salivation, retching, and emesis during motion sickness and vestibular dysfunc­tion in this species. The lack of a convincing projection to the dorsal respiratory group region in the cat is also consistent with the report that dorsal respiratory group lesions in cats do not affect vestibulo-respiratory responses (17).

The subnuclear distribution of vestibulo­parabrachial 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 pic­tured in Figure 2A (case 18RFG). Anterogradely labeled axons often displayed varicosities and terminal bouton­like endings, shown by the arrows. Scalebar: 50 J.tm.

VN-Autonomic Projections

to the pattern in rabbits. Both species display projections to the caudal aspect of the medial parabrachial nucleus, the ventrolateral aspect of the Kolliker-Fuse nucleus, and the external me­dial parabrachial nucleus (9). However, the den­sity of projections to the lateral and the ventro­lateral parabrachial nucleus are considerably more prominent in rats. These regions of the lat­eral parabrachial nucleus receive ascending in­put from the medial subnucleus of NTS and the area postrema (18) and descending input from cerebral cortex and the amygdala (19); they send projections to the hypothalamus (20). Hence, these connections may suggest a greater contribution of vestibular input to neuroendo­crine responses in rats than in rabbits.

The convergence of vestibular and gustatory information in the medial parabrachial nucleus may serve as an neural substrate for the devel­opment of motion-induced conditioned taste aversions, which are a hallmark of motion sick­ness in rats (21). Vestibular projections to the medial parabrachial nucleus include regions that receive ascending gustatory inputs from the rostral aspect of the nucleus of the solitary tract (18,22) and that respond to gustatory and orofa­cial stimuli (23,24). The caudal aspect of the medial parabrachial nucleus also receives gas­trointestinal afferent information via a relay in the medial subnucleus of the nucleus of the soli­tary tract (16,18,25). The importance of this convergence of visceral and gustatory inputs is indicated by the demonstration that the acquisi­tion of conditioned taste aversions (elicited by

7.5

pairing a novel taste with chemical stimuli that elicit gastrointestinal malaise) in rats is im­paired specifically by ablation of the gustatory regions of the parabrachial nucleus (26). These findings raise the hypothesis that a similar inte­gration of gustatory, gastrointestinal, and vesti­bular input in the medial parabrachial nucleus will be essential for the development of motion­induced conditioned taste aversion. This direct convergence may account for the resemblance between motion sickness and responses to in­gestion of toxins (27).

The existence of a network of vestibular nu­clear connections with central autonomic path­ways suggests that vestibular nucleus outputs are an integral part of signal processing in both descending and ascending autonomic pathways. The descending vestibular nuclear projections to the solitary nucleus and the sympathetic and parasympathetic brain stem regions are likely to contribute to the effects of vestibular · stimula­tion on cardiovascular and respiratory control (2,28). However, there is recent evidence that both vestibular and visceral signals contribute to perception of the spatial vertical ( 6) and that a common pattern of space and motion discomfort is reported by patients with vestibular dysfunc­tion, panic disorder with agoraphobia, agorapho­bia without panic, and height phobias (29). Since the parabrachial nucleus is connected recipro­cally with the hypothalfuuus, prefrontal cortex, and amygdala, these vestibulo-parabrachial pro­jections provide a potential neural substrate for perceptual and affective phenomena.

REFERENCES

1. Yates BJ. Miller AD. Properties of sympathetic reflexes elicited by natural vestibular stimulation: implications for cardiovascular control. J Neurophysiol J 994;71 :2087-92.

2. Yates BJ. Vestibular influences on cardiovascular con­trol. In Yates BJ, Miller AD, eds. Vestibular automonic regulation. CRC Press; 1996:97-111.

3. Doba N, Reis DJ. Role of the cerebellum and vestibular apparatus in regulation of orthostatic reflexes in the cat. Cir Res 1974;34:9-18.

4. Uchino Y, Kudo N, Tsuda K, Iwamura Y. Vestibular inhibition of sympathetic nerve activities. Brain Res 1970;22: 195-206.

5. Yates B, Yamagata Y, Bolton P. The ventrolateral medulla of the cat mediates vestibula-sympathetic reflexes. Brain Res 1991;552:265-272.

6. Mittelstaedt H. Somatic graviception. Biol Psychol 1996;42:53-74.

7. Balaban CD. Beryozkin G. Vestibular nucleus projections to nucleus tractus solitarius and the dorsal motor nucleus of the vagus nerve: potential substrates for vestibula­autonomic interactions. Exp Brain Res 1994;98:200-12.

8. Yates BJ, Grelot L, Kerman IA, Balaban CD, Jakus J, Miller AD. The organization of vestibular inputs to nucleus tractus solitarius (NTS) and adjacent structures in the cat brainstem. Am J Physiol 1994;267:R974-R983.

9. Balban CD. Vestibular nucleus projections to the parabrachial nucleus in rabbits; implications for vestib­ular influences on autonomic function. Exp Brain Res 1996; 108:367-81.

10. Saper C, Loewy A. Efferent connections of the parabra­chial nucleus in the rat. Brain Res 1980; 197:291-317.

11. Kalia M, Sullivan M. Brain stem projections of sensory and motor components of the vagus nerve in the rat. J Comp Neurol1982;211:248-64.

76

12. Norgren R. Projections from the nucleus of the solitary tract in the rat. Neurosci 1978;3:207-18.

13. Shapiro RE, Miselis RR. The central organization of the vagus nerve innervating the stomach of the rat. J Comp Neurol1985;238:473-88.

14. Cohen MI. Central determinants of respiratory rhythms. Annu Rev Phsyiol 1981 ;43:91-104.

15. Spiegel EA, Sommer I. Vestibular mechanisms. In: Glasser 0, ed. Medical physics. Chicago: Year Book Publishers; 1994:1638-55.

16. Leslie RA, Gwyn DO, Hopkins DA. The central distri­bution of the cervical vagus nerve and gastric afferent and efferent projections in the rat. Brain Res Bull 1982;8:37-43.

17. Yates BJ, Siniaia MS, Miller AD. Descending path­ways necessary for vestibular int1uences on sympa­thetic and inspiratory outflow. Am J Physiol 1995;268: R1381-Rl385.

18. Herbert H, Moga MM, Saper CB. Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat. J Comp Neurol1990;293:540-80.

19. Moga MM, Herbert H, Hurley KM, Yasui Y, Gray TS, Saper CB. Organization of cortical, basal forebrain and hypothalamic afferents to the parabrachial nucleus in the rat. J Comp Neurol1990;295:624-61.

20. Fulweiler CE, Saper CB. Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat. Brain Res Rev 1984;7:229-59.

21. Ossenkopp KP. Area postrema lesions in rats enhance

J.D.Porterand C.D.B~aban

the magnitude of body rotation-induced conditioned taste aversions. Behav Neural Biol1983;38:82-96.

22. Norgren R, Pfaffman C. The pontine taste area in the rat. Brain Res 197 5 ;91 :99-117.

23. DiLorenzo PM, Schwartzbaum JS. Coding of gustatory information in the pontine parabrachial nuclei of the rabbit: magnitude of the neural response. Brain Res 1982;251 :229-44.

24. DiLorenzo PM, Schwartzbaum JS. Coding of gustatory information in the pontine parabrachial nuclei of the rabbit: temporal patterns of neural response. Brain Res 1982251:245-57.

25. Kalia M, Mesulam M. Brain stem projections of sensory and motor components of the vagus complex in the cat: 2, Laryngeal, tracheobronchial, pulmonary, cardiac and gas­trointestinal branches. J Comp Neuroll980;193:467-508.

26. Spector AC, Norgren R, Grill H. Parabrachial gustatory lesions impair taste aversion learning in rats. Behav Neurosci 1992;106: 147-61.

27. Money KE, Lackner JR, Cheung SK. The autonomic system and motion sickness. In: Yates BJ, Miller AD, eds. Vestibular autonomic regulation. CRC Press; 1996:147-73.

28. Miller AD, Yates BJ. Vestibular effects on respiratory activity. In: Yates BJ, Miller AD, eds. Vestibular auto­nomic regulation, CRC Press; 1996:113-25.

29. Jacob RJ, Furman JM, Perel JM. Panic, phobia and ves­tibular dysfunction. In: Yates BJ, Miller AD, eds. Ves­tibular autonomic regulation, CRC Press; 1996:197-227.