Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats.

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ∼17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.

Mapping of neural pathways that influence diaphragm activity and project to the lumbar spinal cord in cats.

During breathing, the diaphragm and abdominal muscles contract out of phase. However, during other behaviors (including vomiting, postural adjustments, and locomotion) simultaneous contractions are required of the diaphragm and other muscle groups including abdominal muscles. Recent studies in cats using transneuronal tracing techniques showed that in addition to neurons in the respiratory groups, cells in the inferior and lateral vestibular nuclei (VN) and medial pontomedullary reticular formation (MRF) influence diaphragm activity. The goal of the present study was to determine whether neurons in these regions have collateralized projections to both diaphragm motoneurons and the lumbar spinal cord. For this purpose, the transneuronal tracer rabies virus was injected into the diaphragm, and the monosynaptic retrograde tracer Fluoro-Gold (FG) was injected into the Th13-L1 spinal segments. A large fraction of MRF and VN neurons (median of 72 and 91%, respectively) that were infected by rabies virus were dual-labeled by FG. These data show that many MRF and VN neurons that influence diaphragm activity also have a projection to the lumbar spinal cord and thus likely are involved in coordinating behaviors that require synchronized contractions of the diaphragm and other muscle groups.

Effects of postural changes and removal of vestibular inputs on blood flow to and from the hindlimb of conscious felines.

Considerable data show that the vestibular system contributes to blood pressure regulation. Prior studies reported that lesions that eliminate inputs from the inner ears attenuate the vasoconstriction that ordinarily occurs in the hindlimbs of conscious cats during head-up rotations. These data led to the hypothesis that labyrinthine-deficient animals would experience considerable lower body blood pooling during head-up postural alterations. The present study tested this hypothesis by comparing blood flow though the femoral artery and vein of conscious cats during 20-60 degrees head-up tilts from the prone position before and after removal of vestibular inputs. In vestibular-intact animals, venous return from the hindlimb dropped considerably at the onset of head-up tilts and, at 5 s after the initiation of 60 degrees rotations, was 66% lower than when the animals were prone. However, after the animals were maintained in the head-up position for another 15 s, venous return was just 33% lower than before the tilt commenced. At the same time point, arterial inflow to the limb had decreased 32% from baseline, such that the decrease in blood flow out of the limb due to the force of gravity was precisely matched by a reduction in blood reaching the limb. After vestibular lesions, the decline in femoral artery blood flow that ordinarily occurs during head-up tilts was attenuated, such that more blood flowed into the leg. Contrary to expectations, in most animals, venous return was facilitated, such that no more blood accumulated in the hindlimb than when labyrinthine signals were present. These data show that peripheral blood pooling is unlikely to account for the fluctuations in blood pressure that can occur during postural changes of animals lacking inputs from the inner ear. Instead, alterations in total peripheral resistance following vestibular dysfunction could affect the regulation of blood pressure.

Responses of thoracic spinal interneurons to vestibular stimulation.

Vestibular influences on outflow from the spinal cord are largely mediated via spinal interneurons, although few studies have recorded interneuronal activity during labyrinthine stimulation. The present study determined the responses of upper thoracic interneurons of decerebrate cats to electrical stimulation of the vestibular nerve or natural stimulation of otolith organs and the anterior and posterior semicircular canals using rotations in vertical planes. A majority of thoracic interneurons (74/102) responded to vestibular nerve stimulation at median latencies of 6.5 ms (minimum of approximately 3 ms), suggesting that labyrinthine inputs were relayed to these neurons through trisynaptic and longer pathways. Thoracic interneuronal responses to vertical rotations were similar to those of graviceptors such as otolith organs, and a wide array of tilt directions preferentially activated different cells. Such responses were distinct from those of cells in the cervical and lumbar enlargements, which are mainly elicited by ear-down tilts and are synchronous with stimulus position when low rotational frequencies are delivered, but tend to be in phase with stimulus velocity when high frequencies are employed. The dynamic properties of thoracic interneuronal responses to tilts were instead similar to those of thoracic motoneurons and sympathetic preganglionic neurons. However, the preferred tilt directions of the interneurons were more heterogeneous than thoracic spinal outputs, showing that the outputs do not simply reflect an addition of local interneuronal activity.

Responses of rostral fastigial nucleus neurons of conscious cats to rotations in vertical planes.

The rostral fastigial nucleus (RFN) of the cerebellum is thought to play an important role in postural control, and recent studies in conscious nonhuman primates suggest that this region also participates in the sensory processing required to compute body motion in space. The goal of the present study was to examine the dynamic and spatial responses to sinusoidal rotations in vertical planes of RFN neurons in conscious cats, and determine if they are similar to responses reported for monkeys. Approximately half of the RFN neurons examined were classified as graviceptive, since their firing was synchronized with stimulus position and the gain of their responses was relatively unaffected by the frequency of the tilts. The large majority (80%) of graviceptive RFN neurons were activated by pitch rotations. Most of the remaining RFN units exhibited responses to vertical oscillations that encoded stimulus velocity, and approximately 50% of these velocity units had a response vector orientation aligned near the plane of a single vertical semicircular canal. Unlike in primates, few feline RFN neurons had responses to vertical rotations that suggested integration of graviceptive (otolith) and velocity (vertical semicircular canal) signals. These data indicate that the physiological role of the RFN may differ between primates and lower mammals. The RFN in rats and cats in known to be involved in adjusting blood pressure and breathing during postural alterations in the transverse (pitch) plane. The relatively simple responses of many RFN neurons in cats are appropriate for triggering such compensatory autonomic responses.

Responses of caudal vestibular nucleus neurons of conscious cats to rotations in vertical planes, before and after a bilateral vestibular neurectomy.

Although many previous experiments have considered the responses of vestibular nucleus neurons to rotations and translations of the head, little data are available regarding cells in the caudalmost portions of the vestibular nuclei (CVN), which mediate vestibulo-autonomic responses among other functions. This study examined the responses of CVN neurons of conscious cats to rotations in vertical planes, both before and after a bilateral vestibular neurectomy. None of the units included in the data sample had eye movement-related activity. In labyrinth-intact animals, some CVN neurons (22%) exhibited graviceptive responses consistent with inputs from otolith organs, but most (55%) had dynamic responses with phases synchronized with stimulus velocity. Furthermore, the large majority of CVN neurons had response vector orientations that were aligned either near the roll or vertical canal planes, and only 18% of cells were preferentially activated by pitch rotations. Sustained head-up rotations of the body provide challenges to the cardiovascular system and breathing, and thus the response dynamics of the large majority of CVN neurons were dissimilar to those of posturally-related autonomic reflexes. These data suggest that vestibular influences on autonomic control mediated by the CVN are more complex than previously envisioned, and likely involve considerable processing and integration of signals by brainstem regions involved in cardiovascular and respiratory regulation. Following a bilateral vestibular neurectomy, CVN neurons regained spontaneous activity within 24 h, and a very few neurons (<10%) responded to vertical tilts <15 degrees in amplitude. These findings indicate that nonlabyrinthine inputs are likely important in sustaining the activity of CVN neurons; thus, these inputs may play a role in functional recovery following peripheral vestibular lesions.

Consequences of postural changes and removal of vestibular inputs on the movement of air in and out of the lungs of conscious felines.

A variety of experimental approaches in human subjects and animal models established that the vestibular system contributes to regulation of respiration. In cats, the surgical elimination of labyrinthine signals produced changes in the spontaneous activity and posturally related responses of a number of respiratory muscles. However, these effects were complex and sometimes varied between muscle compartments, such that the physiological role of vestibulo-respiratory responses is unclear. The present study determined the functional significance of vestibulo-respiratory influences by examining the consequences of a bilateral labyrinthectomy on breathing rate and the pressure, volume, and flow rate of air exchanged during inspiration and expiration as body orientation with respect to gravity was altered. Data were collected from conscious adult cats acclimated to breathing through a facemask connected to a pneuomotach during 60 degrees head-up pitch and ear-down roll body rotations. Removal of vestibular inputs resulted in a 15% reduction in breathing rate, a 13% decrease in minute ventilation, a 16% decrease in maximal inspiratory airflow rate, and a 14% decrease in the maximal expiratory airflow rate measured when the animals were in the prone position. However, the lesions did not appreciably affect phasic changes in airflow parameters related to alterations in posture. These results suggest that the role of the vestibular system in the control of breathing is to modify baseline respiratory parameters in proportion to the general intensity of ongoing movements, and not to rapidly alter ventilation in accordance with body position.

A monosynaptic pathway links the vestibular nuclei and masseter muscle motoneurons in rats.

Physiological evidence indicates that vestibular signals modulate the activity of motoneurons innervating the masseter muscle. Recently, experiments using transynaptic retrograde transport of pseudorabies virus provided anatomical evidence that many neurons concentrated in the dorsomedial part of the parvicellular division of the medial vestibular nucleus (MVePC) and the caudal prepositus hypoglossi (PH) provide inputs to motoneurons innervating the lower third of the superficial layer of the masseter muscle. However, it was not clear whether this vestibulo-trigeminal projection was monosynaptic or polysynaptic. The present study sought to determine whether neurons in the MVePC or PH project directly to motoneurons controlling the masseter muscle in rats. For this purpose, an anterograde tracer (biotinylated dextran amine, BDA) was injected into vestibular nuclei (mainly MVePC) or PH and a retrograde tracer (the beta-subunit of cholera toxin, b-CT) was injected into the masseter muscle ipsilateral or contralateral to the BDA injection site. Following injections of BDA into the vestibular nuclei or PH, anterogradely labeled axon terminals were observed bilaterally in the motor trigeminal nucleus (Mo5), particularly in the ventral, medial, and lateral portions of the nucleus; projections to dorsal Mo5 were sparse. In addition, retrogradely labeled motoneurons were located in the ventral and lateral portions of the ipsilateral Mo5. Moreover, anterogradely labeled terminals were observed to be in close proximity to motoneurons in the Mo5 that were retrogradely labeled from b-CT injections into the masseter muscle. This study provides direct evidence that a monosynaptic pathway exists between the MVePC and PH and masseter motoneurons.

Transneuronal tracing of neural pathways that regulate hindlimb muscle blood flow.

Despite considerable interest in the neural mechanisms that regulate muscle blood flow, the descending pathways that control sympathetic outflow to skeletal muscles are not adequately understood. The present study mapped these pathways through the transneuronal transport of two recombinant strains of pseudorabies virus (PRV) injected into the gastrocnemius muscles in the left and right hindlimbs of rats: PRV-152 and PRV-BaBlu. To prevent PRV from being transmitted to the brain stem via motor circuitry, a spinal transection was performed just below the L2 level. Infected neurons were observed bilaterally in all of the areas of the brain that have previously been shown to contribute to regulating sympathetic outflow: the medullary raphe nuclei, rostral ventrolateral medulla (RVLM), rostral ventromedial medulla, A5 adrenergic cell group region, locus coeruleus, nucleus subcoeruleus, and the paraventricular nucleus of the hypothalamus. The RVLM, the brain stem region typically considered to play the largest role in regulating muscle blood flow, contained neurons infected following the shortest postinoculation survival times. Approximately half of the infected RVLM neurons were immunopositive for tyrosine hydroxylase, indicating that they were catecholaminergic. Many (47%) of the RVLM neurons were dually infected by the recombinants of PRV injected into the left and right hindlimb, suggesting that the central nervous system has a limited capacity to independently regulate blood flow to left and right hindlimb muscles.

Vestibular inputs elicit patterned changes in limb blood flow in conscious cats.

Previous experiments have demonstrated that the vestibular system contributes to regulating sympathetic nervous system activity, particularly the discharges of vasoconstrictor fibres. In the present study, we examined the physiological significance of vestibulosympathetic responses by comparing blood flow and vascular resistance in the forelimb and hindlimb during head-up tilt from the prone position before and after the removal of vestibular inputs through a bilateral vestibular neurectomy. Experiments were performed on conscious cats that were trained to remain sedentary on a tilt table during rotations up to 60 deg in amplitude. Blood flow through the femoral and brachial arteries was recorded during whole-body tilt using perivascular probes; blood pressure was recorded using a telemetry system and vascular resistance was calculated from blood pressure and blood flow measurements. In vestibular-intact animals, 60 deg head-up tilt produced approximately 20% decrease in femoral blood flow and approximately 37% increase in femoral vascular resistance relative to baseline levels before tilt; similar effects were also observed for the brachial artery ( approximately 25% decrease in blood flow and approximately 38% increase in resistance). Following the removal of vestibular inputs, brachial blood flow and vascular resistance during head-up tilt were almost unchanged. In contrast, femoral vascular resistance increased only approximately 6% from baseline during 60 deg head-up rotation delivered in the first week after elimination of vestibular signals and approximately 16% in the subsequent 3-week period (as opposed to the approximately 37% increase in resistance that occurred before lesion). These data demonstrate that vestibular inputs associated with postural alterations elicit regionally specific increases in vascular resistance that direct blood flow away from the region of the body where blood pooling may occur. Thus, the data support the hypothesis that vestibular influences on the cardiovascular system serve to protect against the occurrence of orthostatic hypotension.

Effects of postural changes and removal of vestibular inputs on blood flow to the head of conscious felines.

Prior studies have shown that removal of vestibular inputs produces lability in blood pressure during orthostatic challenges (Holmes MJ, Cotter LA, Arendt HE, Cass SP, and Yates BJ. Brain Res 938: 62-72, 2002; Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999). Furthermore, these studies led to the prediction that the blood pressure instability results in susceptibility for orthostatic intolerance. The present experiments tested this hypothesis by recording common carotid blood flow (CCBF) in conscious cats during head-up tilts of 20, 40, and 60 degrees amplitudes, before and after the surgical elimination of labyrinthine inputs through a bilateral vestibular neurectomy. Before vestibular lesions in most animals, CCBF remained stable during head-up rotations. Unexpectedly, in five of six animals, the vestibular neurectomy resulted in a significant increase in baseline CCBF, particularly when the laboratory was illuminated; on average, basal blood flow measured when the animals were in the prone position was 41 +/- 17 (SE) % higher after the first week after the lesions. As a result, even when posturally related lability in CCBF occurred after removal of vestibular inputs, blood supply to the head was not lower than when labyrinthine inputs were present. These data suggest that vestibular influences on cardiovascular regulation are more complex than previously appreciated, because labyrinthine signals appear to participate in setting basal rates of blood flow to the head in addition to triggering dynamic changes in the circulation to compensate for orthostatic challenges.

Vestibular inputs to propriospinal interneurons in the feline C1-C2 spinal cord projecting to the C5-C6 ventral horn.

The resting length of respiratory muscles must be altered during changes in posture in order to maintain stable ventilation. Prior studies showed that although the vestibular system contributes to these adjustments in respiratory muscle activity, the medullary respiratory groups receive little vestibular input. Additionally, previous transneuronal tracing studies demonstrated that propriospinal interneurons in the C(1)-C(2) spinal cord send projections to the ipsilateral diaphragm motor pool. The present study tested the hypothesis that C(1)-C(2) interneurons mediate vestibular influences on diaphragm activity. Recordings were made from 145 C(1)-C(2) neurons that could be antidromically activated from the ipsilateral C(5)-C(6 )ventral horn, 60 of which had spontaneous activity, during stimulation of vestibular receptors using electric current pulses or whole-body rotations in vertical planes. The firing of 19 of 31 spontaneously active neurons was modulated by vertical vestibular stimulation; the response vector orientations of many of these cells were closer to the pitch plane than the roll plane, and their response gains remained relatively constant across stimulus frequencies. Virtually all spontaneously active neurons responded robustly to electrical vestibular stimulation, and their response latencies were typically shorter than those for diaphragm motoneurons. Nonetheless, respiratory muscle responses to vestibular stimulation were still present after inactivation of the C(1)-C(2) cord using large injections of either muscimol or ibotenic acid. These data suggest that C(1)-C(2) propriospinal interneurons contribute to regulating posturally related responses of the diaphragm, although additional pathways are also involved in generating this activity.

Transneuronal tracing of vestibulo-trigeminal pathways innervating the masseter muscle in the rat.

Previous studies reported that the activity of trigeminal motoneurons innervating masseter muscles is modulated by vestibular inputs. We performed the present study to provide an anatomical substrate for these physiological observations. The transynaptic retrograde tracer pseudorabies virus-Bartha was injected into multiple sites of the lower third of the superficial layer of the masseter muscle in rats, a subset of which underwent a sympathectomy prior to virus injections, and the animals were euthanized 24-120 h later. Labeled masseteric motoneurons were first found in the ipsilateral trigeminal motor nucleus following a 24-h postinoculation period; subsequent to 72-h survival times, the number of infected motoneurons increased, and at > or =96 h many of these cells showed signs of cytopathic changes. Following 72-h survival times, a few transynaptically labeled neurons appeared bilaterally in the medial vestibular nucleus (MVe) and the caudal prepositus hypoglossi (PH) and in the ipsilateral spinal vestibular nucleus (SpVe). At survival times of 96-120 h, labeled neurons were consistently observed bilaterally in all vestibular nuclei (VN), although the highest concentration of infected cells was located in the caudal part of the MVe, the SpVe, and the caudal portion of PH. The distribution and density of labeling in the VN and PH were similar in sympathectomized and nonsympathectomized rats. These anatomical data provide the first direct evidence that neurons in the VN and PH project bilaterally to populations of motoneurons innervating the lower third of the superficial layer of the masseter muscle. The MVe, PH, and SpVe appear to play a predominant integrative role in producing vestibulo-trigeminal responses.

Afferent pathways to the region of the vestibular nuclei that participates in cardiovascular and respiratory control.

Prior experiments have shown that a region of the medial and inferior vestibular nuclei contributes to cardiovascular and respiratory regulation. In addition to labyrinthine inputs, the majority of neurons in this region of the vestibular nuclei receive signals from the skin, muscle, and viscera, although the pathways conveying these nonlabyrinthine inputs to the vestibular nucleus neurons are unknown. To gain further insight into the afferent pathways to this functionally distinct subdivision of the vestibular complex, we combined monosynaptic mapping with viral transneuronal tracing in the ferret. First order afferent projections were defined by retrograde transport of the beta-subunit of cholera toxin (CTbeta), and the extended polysynaptic circuitry was defined in the same animals by injection of a recombinant of pseudorabies virus Bartha (PRV) into the contralateral vestibular nuclei. Neurons containing CTbeta or infected by retrograde transneuronal transport and replication of PRV were distributed throughout the spinal cord, but were 10 times more prevalent in the cervical cord than the lumbar cord. The labeled spinal neurons were most commonly observed in Rexed's laminae IV-VI and the dorsal portions of laminae VII-VIII. Both the CTbeta and PRV injections also resulted in labeling of neurons in all four vestibular nuclei, the prepositus hypoglossi, the reticular formation, the inferior olivary nucleus, the medullary raphe nuclei, the spinal and principal trigeminal nuclei, the facial nucleus, and the lateral reticular nucleus. Following survival times >/=3 days, PRV-infected neurons were additionally present in nucleus solitarius and the gracile and cuneate nuclei. These data show that an anatomical substrate is present for somatosensory and visceral inputs to influence the activity of cells in the autonomic region of the vestibular nuclei and suggest that these signals are primarily transmitted through brainstem relay neurons.

Polysynaptic pathways from the vestibular nuclei to the lateral mammillary nucleus of the rat: substrates for vestibular input to head direction cells.

The activity of some neurons in the lateral mammillary nucleus (LMN) of the rat corresponds with the animal's current head direction (HD). HD cells have been studied extensively but the circuitry responsible for the generation and maintenance of the HD signal has not been established. The present study tested the hypothesis that a polysynaptic pathway connects the vestibular nuclei with the LMN via one or more relay nuclei. This circuitry could provide a substrate for the integration of sensory input necessary for HD cell activity. This hypothesis is based upon the prior demonstration that labyrinthectomy abolishes HD selectivity in thalamic neurons. Viral transneuronal tracing with pseudorabies virus (PRV) was used to test this hypothesis. We injected recombinants of PRV into the LMN and surrounding nuclei of adult male rats and defined the patterns of retrograde transneuronal infection at survival intervals of 60 and 72 h. Infected medial vestibular neurons (MVN) were only observed at the longest postinoculation interval in animals in which the injection site was localized largely to the LMN. Robust infection of the dorsal tegmental nucleus (DTN) and nucleus prepositus hypoglossi (PH) in these cases, but not in controls, at both survival intervals identified these nuclei as potential relays of vestibular input to the LMN. These data are consistent with the conclusion that vestibular information that contributes to the LMN HD cell activity is relayed to this caudal hypothalamic cell group via a polysynaptic brainstem circuit.

Effects of bilateral vestibular nucleus lesions on cardiovascular regulation in conscious cats.

The vestibular system participates in cardiovascular regulation during postural changes. In prior studies (Holmes MJ, Cotter LA, Arendt HE, Cas SP, and Yates BJ. Brain Res 938: 62-72, 2002, and Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999), transection of the vestibular nerves resulted in instability in blood pressure during nose-up body tilts, particularly when no visual information reflecting body position in space was available. However, recovery of orthostatic tolerance occurred within 1 wk, presumably because the vestibular nuclei integrate a variety of sensory inputs reflecting body location. The present study tested the hypothesis that lesions of the vestibular nuclei result in persistent cardiovascular deficits during orthostatic challenges. Blood pressure and heart rate were monitored in five conscious cats during nose-up tilts of varying amplitude, both before and after chemical lesions of the vestibular nuclei. Before lesions, blood pressure remained relatively stable during tilts. In all animals, the blood pressure responses to nose-up tilts were altered by damage to the medial and inferior vestibular nuclei; these effects were noted both when animals were tested in the presence and absence of visual feedback. In four of the five animals, the lesions also resulted in augmented heart rate increases from baseline values during 60 degrees nose-up tilts. These effects persisted for longer than 1 wk, but they gradually resolved over time, except in the animal with the worst deficits. These observations suggest that recovery of compensatory cardiovascular responses after loss of vestibular inputs is accomplished at least in part through plastic changes in the vestibular nuclei and the enhancement of the ability of vestibular nucleus neurons to discriminate body position in space by employing nonlabyrinthine signals.

Responses of feline medial medullary reticular formation neurons with projections to the C5-C6 ventral horn to vestibular stimulation.

Prior studies have shown that the vestibular system contributes to adjusting respiratory muscle activity during changes in posture, and have suggested that portions of the medial medullary reticular formation (MRF) participate in generating vestibulo-respiratory responses. However, there was previously no direct evidence to demonstrate that cells in the MRF relay vestibular signals monosynaptically to respiratory motoneurons. The present study tested the hypothesis that the firing of MRF neurons whose axons could be antidromically activated from the vicinity of diaphragm motoneurons was modulated by whole-body rotations in vertical planes that stimulated vestibular receptors, as well as by electrical current pulses delivered to the vestibular nerve. In total, 171 MRF neurons that projected to the C5-C6 ventral horn were studied; they had a conduction velocity of 34+/-15 (standard deviation) m/sec. Most (135/171 or 79%) of these MRF neurons lacked spontaneous firing. Of the subpopulation of units with spontaneous discharges, only 3 of 20 cells responded to vertical rotations up to 10 degrees in amplitude, whereas the activity of 8 of 14 neurons was affected by electrical stimulation of the vestibular nerve. These data support the hypothesis that the MRF participates in generating vestibulo-respiratory responses, but also suggest that some neurons in this region have other functions.

Effects of postural changes and vestibular lesions on genioglossal muscle activity in conscious cats.

Previous studies in humans showed that genioglossal muscle activity is higher when individuals are supine than when they are upright, and prior experiments in anesthetized or decerebrate animals suggested that vestibular inputs might participate in triggering these alterations in muscle firing. The present study determined the effects of whole body tilts in the pitch (nose-up) plane on genioglossal activity in a conscious feline model and compared these responses with those generated by roll (ear-down) tilts. We also ascertained the effects of a bilateral vestibular neurectomy on the alterations in genioglossal activity elicited by changes in body position. Both pitch and roll body tilts produced modifications in muscle firing that were dependent on the amplitude of the rotation; however, the relative effects of ear-down and nose-up tilts on genioglossal activity were variable from animal to animal. The response variability observed might reflect the fact that genioglossus has a complex organization and participates in a variety of tongue movements; in each animal, electromyographic recordings presumably sampled the firing of different proportions of fibers in the various compartments and subcompartments of the muscle. Furthermore, removal of labyrinthine inputs resulted in alterations in genioglossal responses to postural changes that persisted until recordings were discontinued approximately 1 mo later, demonstrating that the vestibular system participates in regulating the muscle's activity. Peripheral vestibular lesions were subsequently demonstrated to be complete through the postmortem inspection of temporal bone sections or by observing that vestibular nucleus neurons did not respond to rotations in vertical planes.

Use of electrical vestibular stimulation to alter genioglossal muscle activity in awake cats.

Prior work has shown that the vestibular system contributes to regulating activity of upper airway muscles including the tongue protruder muscle genioglossus. The goal of the present experiments was to determine whether electrical vestibular stimulation could potentially be used to alter genioglossal activity in awake animals. Six adult cats were instrumented for recording of EMG activity from genioglossus, abdominal musculature, and triceps. In addition, a silver ball electrode was implanted on the round window for stimulation of vestibular afferents. Subsequently, stimulation and recordings were conducted while animals were awake. In all cases, stimulation using single shocks or trains of pulses > 100 microA in intensity produced responses in all muscles, including genioglossus. The latency of the genioglossal response was approximately 12 msec, and delivering continuous current trains to the labyrinth chronically elevated the muscle's activity. Although a number of muscles were affected by the stimulus, animals experienced no obvious distress or balance disturbances. Vestibular stimulation remained effective in producing genioglossal responses until experiments were discontinued 1-2 months following onset. These data suggest that electrical vestibular stimulation could potentially be used therapeutically to alter upper airway muscle activity.