Overview

Vestibular balance of food intake (2014)

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The intake of the nutrients is under complex control involving signals from both the periphery and central nervous system The purpose of this article is to review research reports related to vestibular stimulation and its role in regulation of food intake and to suggest translational research in this area. Vestibular system is having extensive interactions with hypothalamus, dorsal raphe nucleus, nucleus tractus solitarius, locus coeruleus, hippocampal formation and regulates food intake. The present review provides evidence for the relationship between vestibular stimulation and food intake. Understanding these associations will be important in developing effective treatments for obesity and related metabolic diseases.

International Journal of Pharma and Bio Sciences

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Appetite Centre

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus (1997)

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We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Department of Otorhinolaryngology, Faculty of MedicineKyushu University, Fukuoka, Japan

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Medial vestibular connections with the hypocretin (orexin) system (2005)

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The mammalian medial vestibular nucleus (MVe) receives input from all vestibular endorgans and provides extensive projections to the central nervous system. Recent studies have demonstrated projections from the MVe to the circadian rhythm system. In addition, there are known projections from the MVe to regions considered to be involved in sleep and arousal. In this study, afferent and efferent subcortical connectivity of the medial vestibular nucleus of the golden hamster (Mesocricetus auratus) was evaluated using cholera toxin subunit-B (retrograde), Phaseolus vulgaris leucoagglutinin (anterograde), and pseudorabies virus (transneuronal retrograde) tract-tracing techniques. The results demonstrate MVe connections with regions mediating visuomotor and postural control, as previously observed in other mammals. The data also identify extensive projections from the MVe to regions mediating arousal and sleep-related functions, most of which receive immunohistochemically identified projections from the lateral hypothalamic hypocretin (orexin) neurons. These include the locus coeruleus, dorsal and pedunculopontine tegmental nuclei, dorsal raphe, and lateral preoptic area. The MVe itself receives a projection from hypocretin cells. CTB tracing demonstrated reciprocal connections between the MVe and most brain areas receiving MVe efferents. Virus tracing confirmed and extended the MVe afferent connections identified with CTB and additionally demonstrated transneuronal connectivity with the suprachiasmatic nucleus and the medial habenular nucleus. These anatomical data indicate that the vestibular system has access to a broad array of neural functions not typically associated with visuomotor, balance, or equilibrium, and that the MVe is likely to receive information from many of the same regions to which it projects.

Department of Psychiatry, Stony Brook University, Stony Brook, New York 11794, USA.

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Vestibular influences on the autonomic nervous system (1996)

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Considerable evidence exists to suggest that both sympathetic and respiratory outflow from the central nervous system are influenced by the vestibular system. Otolith organs that respond to pitch rotations seem to play a predominant role in producing vestibulo-sympathetic and vestibulo-respiratory responses in cats. Because postural changes involving nose-up pitch challenge the maintenance of stable blood pressure and blood oxygenation in this species, vestibular effects on the sympathetic and respiratory systems are appropriate to participate in maintaining homeostasis during movement. Vestibular influences on respiration and circulation are mediated by a relatively small portion of the vestibular nuclear complex comprising regions in the medial and inferior vestibular nuclei just caudal to Deiters’ nucleus. Vestibular signals are transmitted to sympathetic preganglionic neurons in the spinal cord through pathways that typically regulate the cardiovascular system. In contrast, vestibular effects on respiratory motoneurons are mediated in part by neural circuits that are not typically involved in the generation of breathing.

Department of Otolaryngology, University of Pittsburgh, Pennsylvania 15213, USA.

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Vestibular influences on the sympathetic nervous system (1996)

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Studies using both electrical and natural stimulation have established that the vestibular system has prominent effects on sympathetic outflow and blood pressure. Preliminary evidence suggests that receptors in both otolith organs and semicircular canals are involved in producing these effects. Furthermore, vestibulosympathetic reflexes appear to be mediated by the medial vestibular nucleus and slowly conducting projections from the rostral ventrolateral medulla and caudal medullary raphe nuclei to preganglionic neurons in the thoracic spinal cord. However, many details are missing from our knowledge and understanding of the functional significance and neural substrate of vestibular influences on the sympathetic nervous system.

Department of Otolaryngology, University of Pittsburgh, Pennsylvania 15213, USA

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Integrative responses of neurons in nucleus tractus solitarius to visceral afferent stimulation and vestibular stimulation in vertical planes (2011)

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Anatomical studies have demonstrated that the vestibular nuclei project to nucleus tractus solitarius (NTS), but little is known about the effects of vestibular inputs on NTS neuronal activity. Furthermore, lesions of NTS abolish vomiting elicited by a variety of different triggering mechanisms, including vestibular stimulation, suggesting that emetic inputs may converge on the same NTS neurons. As such, an emetic stimulus that activates gastrointestinal (GI) receptors could alter the responses of NTS neurons to vestibular inputs. In the present study, we examined in decerebrate cats the responses of NTS neurons to rotations of the body in vertical planes before and after the intragastric administration of the emetic compound copper sulfate. The activity of more than one-third of NTS neurons was modulated by vertical vestibular stimulation, with most of the responsive cells having their firing rate altered by rotations in the head-up or head-down directions. These responses were aligned with head position in space, as opposed to the velocity of head movements. The activity of NTS neurons with baroreceptor, pulmonary, and GI inputs could be modulated by vertical plane rotations. However, injection of copper sulfate into the stomach did not alter the responses to vestibular stimulation of NTS neurons that received GI inputs, suggesting that the stimuli did not have additive effects. These findings show that the detection and processing of visceral inputs by NTS neurons can be altered in accordance with the direction of ongoing movements.

American Journal of Physiology

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Neurovestibular modulation of circadian and homeostatic regulation: Vestibulohypothalamic connection? (2002)

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Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (Tb), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL/6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in Tb and an attenuated Tb circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice. In contrast, the het mice did not exhibit a decrease in mean Tb and only a slight decrease in Tb circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

National Academy of Sciences

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Effects of stimulation of the vestibular nuclei on posterior hypothalamic neuron activity in guinea pigs (1994)

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To clarify the differences among the four main vestibular nuclei in the vestibulo-autonomic reflex, we examined the effects of electrical stimulation of superior, lateral, medial and descending vestibular nuclei (SVN, LVN, MVN and DVN) on posterior hypothalamic area (PHA) neurons in the guinea pig. Ipsi- and contralateral SVN stimulation produced excitation in 30% and 25% of the PHA neurons tested, respectively. Twenty percent of the PHA neurons showed an excitatory response to ipsilateral LVN stimulation while 60% of the neurons tested responded to contralateral LVN stimulation, including excitation of 36% and inhibition of 24%. MVN and DVN stimulation produced little change in PHA neuron activity. These findings suggest that vestibular information processed in the SVN and the LVN is conveyed to the hypothalamus and may then contribute to activation of the vestibulo-autonomic reflex.

Department of Otorhinolaryngology, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan

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Vestibular-mediated increase in central serotonin plays an important role in hypergravity-induced hypophagia in rats (2010)

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Exposure to a hypergravity environment induces acute transient hypophagia, which is partially restored by a vestibular lesion (VL), suggesting that the vestibular system is involved in the afferent pathway of hypergravity-induced hypophagia. When rats were placed in a 3-G environment for 14 days, Fos-containing cells increased in the paraventricular hypothalamic nucleus, the central nucleus of the amygdala, the medial vestibular nucleus, the raphe nucleus, the nucleus of the solitary tract, and the area postrema. The increase in Fos expression was completely abolished or significantly suppressed by VL. Therefore, these regions may be critical for the initiation and integration of hypophagia. Because the vestibular nucleus contains serotonergic neurons and because serotonin (5-HT) is a key neurotransmitter in hypophagia, with possible involvement in motion sickness, we hypothesized that central 5-HT increases during hypergravity and induces hypophagia. To examine this proposition, the 5-HT concentrations in the cerebrospinal fluid were measured when rats were reared in a 3-G environment for 14 days. The 5-HT concentrations increased in the hypergravity environment, and these increases were completely abolished in rats with VL. Furthermore, a 5-HT(2A) antagonist (ketanserin) significantly reduced 3-G (120 min) load-induced Fos expression in the medial vestibular nucleus, and chronically administered ketanserin ameliorated hypergravity-induced hypophagia. These results indicate that hypergravity induces an increase in central 5-HT via the vestibular input and that this increase plays a significant role in hypergravity-induced hypophagia. The 5-HT(2A) receptor is involved in the signal transduction of hypergravity stress in the vestibular nucleus.

Department of Physiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.

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Evidence for vestibular regulation of autonomic functions in a mouse genetic model (2002)

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Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3b/Pou4f3). The only known phenotype of the Brn-3.1−/− mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1−/− mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1−/− mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

National Academy of Sciences

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Projections from the vestibular nuclei to the hypothalamic paraventricular nucleus: morphological evidence for the existence of a vestibular stress pathway in the rat brain (2003)

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Although it has been reported by several laboratories that vestibular stress activates the hypothalamo-pituitary-adrenocortical axis (HPA), the existence of neuronal connections between vestibular and hypothalamic paraventricular neurons has not yet been demonstrated. By the use of a virus-based retrograde trans-synaptic tracing technique in the rat, here we demonstrate vestibular projections to the paraventricular nucleus (PVN). Pseudorabies virus (Bartha strain, type BDR62) was injected into the PVN, and the progression of the infection along synaptically connected neurons was followed in the pons and the medulla, 3 and 4 days post-inoculation. Virus-infected neurons were revealed mainly in the medial vestibular nucleus. Labeled cells were scattered in the spinal, and very rarely in the superior nuclei, but none of them in the lateral vestibular nucleus. Injections of cholera toxin B subunit, a monosynaptic retrograde tracer into the PVN failed to label any cells in the vestibular nuclei. These results provide anatomical evidence for the existence of a vestibulo-paraventricular polysynaptic pathway and support the view that the HPA axis is modulated by vestibular stress.

Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Semmelweis University and the Hungarian Academy of Sciences, Tüzoltó-utca 58, 1094, Budapest, Hungary.

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Responses of hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in the rabbit (1999)

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Acute experiments were performed on rabbits to study the responses of neurons in the anterior, ventromedial, and posterior nuclei of the hypothalamus to single, paired, and rhythmic stimulation of the vestibular nerve and lateral vestibular nucleus of Deiters. The data obtained showed that neurons of the posterior nucleus of the hypothalamus were the most sensitive. Three types of response were seen from hypothalamic neurons, with short, long, and intermediate latent periods. This provides evidence that ascending afferent spike activity from the lateral vestibular nucleus of Deiters to the hypothalamus is mediated by mono-, oligo-, and polysynaptic pathways.

Department of Human and Animal Physiology, Erevan State University, Armenia.

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Effect of chronic centrifugation on body composition in the rat (1972)

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Two groups of adult female rats were chronically centrifuged for 60 days (2.76 G, 4.15 G, controls at 1.00 G). Live weights of centrifugal rats decreased about 20 g (6%) per Delta 1 G above control. This weight loss comprised reductions in both body fat and fat-free body weight (FFBW) as determined by body-composition studies on eight rats per group killed at the end of centrifugation. Of nine components constituting the FFBW, only skeletal muscle, liver, and heart changed significantly in weight. Chemical composition showed reductions (compared with controls) in the fat fraction of most components and increases in the water fraction of liver and gut. Identical measurements were made on the remaining eight rats per group killed 43 days after return to 1 G. Neither centrifuged group had reached the control body-weight level at this time. No statistically significant effect of previous G level was found in any of the body-composition parameters. The possible involvment of physiological regulation was considered.

American Journal of Physiology

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Fullness Centre

Integrative responses of neurons in nucleus tractus solitarius to visceral afferent stimulation and vestibular stimulation in vertical planes (2011)

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Anatomical studies have demonstrated that the vestibular nuclei project to nucleus tractus solitarius (NTS), but little is known about the effects of vestibular inputs on NTS neu ronal activity. Furthermore, lesions of NTS abolish vomiting elicited by a variety of different triggering mechanisms, including vestibular stimulation, suggesting that emetic inputs may converge on the same NTS neurons. As such, an emetic stimulus that activates gastrointestinal (GI) receptors could alter the responses of NTS neurons to vestibular inputs. In the present study, we examined in decerebrate cats the responses of NTS neurons to rotations of the body in vertical planes before and after the intragastric administration of the emetic compound copper sulfate. The activity of more than one-third of NTS neurons was modulated by vertical vestibular stimulation, with most of the responsive cells having their firing rate altered by rotations in the head-up or head-down directions. These responses were aligned with head position in space, as opposed to the velocity of head movements. The activity of NTS neurons with baroreceptor, pulmonary, and GI inputs could be modulated by vertical plane rotations. However, injection of copper sulfate into the stomach did not alter the responses to vestibular stimulation of NTS neurons that received GI inputs, suggesting that the stimuli did not have additive effects. These findings show that the detection and processing of visceral inputs by NTS neurons can be altered in accordance with the direction of ongoing movements.

American Journal of Physiology

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Vestibular nucleus projections to nucleus tractus solitarius and the dorsal motor nucleus of the vagus nerve: potential substrates for vestibulo-autonomic interactions (1993)

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Autonomic effects of vestibular stimulation are important components of phenomena as diverse as acute vestibular dysfunction and motion sickness. How ever, the organization of neural circuits mediating these responses is poorly understood. This study presents evidence for direct vestibular nucleus projections to brain stem regions that mediate autonomic function. One group of albino rabbits received injections of Phaseolus vulgaris leucoagglutinin into the vestibular nuclei. The tracer was visualized immunocytochemically with standard techniques. Anterogradely labeled axons from the caudal medial vestibular nucleus (cMVN) and inferior vestibular nucleus (IVN) could be traced bilaterally to nucleus tractus solitarius (NTS). Fewer axons ended near the somata of neurons in the dorsal motor nucleus of the vagus nerve (DMX). A second group of rabbits received pressure or iontophoretic injections of cholera toxin B-HRP or Fluoro-Gold into a region including NTS and DMX. Retrogradely labeled neurons were observed bilaterally in the caudal half of cMVN and ipsilaterally in IVN. The labeled somata were small and they tended to occupy the center of cMVN in transverse sections. These previously unreported vestibular nucleus projections to NTS and DMX are a potential substrate for vestibular influences on autonomic function. In particular, they may contribute to both cardiovascular control during head movements (e.g., orthostatic reflexes) and autonomic manifestions of vestibular dysfunction, motion sickness and exposure to altered gravitational environments.

Department of Otolaryngology, University of Pittsburgh, The Eye and Ear Institute, Pittsburgh, USA

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Organization of vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem (1994)

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The vestibular system is involved in maintaining stable blood pressure and respiration during changes in posture and is essential for eliciting motion sickness-related vomiting. Because the nucleus tractus solitarius (NTS) participates in the regulation of sympathetic and inspiratory outflow and the triggering of emesis, we tested the hypothesis that this region receives vestibular inputs in cats. In one set of experiments, microinjections of the tracer Phaseolus vulgaris leucoagglutinin into the medial and inferior vestibular nuclei labeled projections to the middle and lateral regions of the NTS. In electrophysiological experiments, electrical stimulation of the vestibular nerve modified the firing rates of neurons located in the same regions. Some neurons with vestibular inputs received convergent signals from the abdominal vagus nerve and could potentially mediate motion sickness-related vomiting. Others received convergent baroreceptor inputs and could act as a substrate for some components of vestibulosympathetic reflexes. In contrast, inspiratory neurons in the dorsal respiratory group received little vestibular input, suggesting that vestibulorespiratory reflexes are mediated by cells located elsewhere.

The American journal of physiology

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Cravings Centre

Vestibular nucleus projections to the parabrachial nucleus in rabbits: implications for vestibular influences on the autonomic nervous system (1996)

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Acute vestibular dysfunction and motion sickness are characterized by autonomic effects such as pallor, nausea, and vomiting. Previous anatomic and physiologic studies suggest that one potential mediator of these effects may be light, direct vestibular nuclear projections to the nucleus tractus solitarius and the dorsal motor nucleus of the vagus nerve. This study presents evidence for relatively dense, direct projections from the vestibular nuclei to the parabrachial nucleus. Male albino rabbits received injections of Phaseolus vulgaris leucoagglutinin into the vestibular nuclei. The tracer was visualized immunocytochemically with standard techniques. Anterogradely labeled axons were traced bilaterally from the vestibular nuclei to the parabrachial nuclear complex, where they terminated around somata in the Kölliker-Fuse nucleus, external medial parabrachial nucleus, medial parabrachial nucleus, and lateral parabrachial nucleus. Less dense terminations were observed in the ventrolateral aspect of the medullary reticular formation, the subtrigeminal nucleus, lateral tegmental field, and nucleus ambiguus. These findings have several important implications. First, they suggest that vestibular input converges directly at brain stem levels with visceral sensory input in both nucleus of the solitary tract and the parabrachial complex. Second, they suggest that vestibular input influences brain stem autonomic outflow via two parallel pathways: (1) direct, light projections to the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and ventrolateral medullary reticular formation; and (2) denser projection to regions of the parabrachial nucleus that project to these brain stem regions. Finally, since the parabrachial nucleus regions that receive vestibular input also project to the hypothalamus and the insular and infralimbic prefrontal cortex, the parabrachial nucleus may serve as an important relay and integrative structure for the cognitive impairment and vegetative symptoms associated with motion sickness, vestibular dysfunction, and responses to altered gravitational environments.

Department of Otolaryngology, University of Pittsburgh, PA 15213, USA.

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Connections between the vestibular nuclei and brain stem regions that mediate autonomic function in the rat (1997)

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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 vestibular 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 Kolliker-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.

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Commentary on: Efferent connections of the parabrachial nucleus in the rat. C.B. Saper and A.D. Loewy, Brain Research 197:291-317, 1980 (2016)

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By the late 1970׳s, the pathways had been identified from neurons in the nucleus of the solitary tract that control visceral sensory inflow and from the paraventricular nucleus and lateral hypothalamus that directly innervate the autonomic preganglionic neurons, thereby controlling autonomic outflow. However, the connections between the two were not yet clear. This paper identified the parabrachial nucleus as a key intermediary, receiving the bulk of outflow from the nucleus of the solitary tract and distributing it to a set of brainstem and forebrain sites that constituted a central autonomic control network. This work also identified the insular cortex as a key visceral sensory cortical area. This article is part of a Special Issue entitled SI:50th Anniversary Issue.

University of Pittsburgh, Department of Otolaryngology, PA 15213, USA

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Clinical Trial

Vestibular Stimulation to Trigger Adipose Loss Clinical Trial (VeSTAL) (2017)

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There is an ongoing and worsening problem with obesity in the developed, and much of the developing world. Although it has long been realized that Western diets that are rich in sugar and fat play an important role in this, it has only recently been realized that exposure to these diets, particularly in childhood, can damage the part of the brain that determines how much fat there is in the body. The result of this damage is that the so-called “set-point” for fat in this part of the brain is pushed upwards. There is a lot of evidence from animals that activating the brain’s balance (vestibular) system pushes this set-point for fat downwards to cause fat loss, probably because this tricks the brain into thinking that the animal is more physically active. The aim of this study is to see whether the same effect can be triggered in humans by non-invasively stimulating the vestibular system with a small electrical current through the skin behind their ears.

University of California, San Diego

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