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Biomedical subjects

B J Yates

Publications and source records attributed to B J Yates.

At least 37 records · Page 2Linked to original sources

Does the vestibular system contribute to head direction cell activity in the rat?

Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.

Animals↗

Transneuronal tracing of neural pathways controlling abdominal musculature in the ferret.

Abdominal musculature participates in generating a large number of behaviors and protective reflexes, although each abdominal muscle is frequently activated differentially during particular motor responses. For example, rectus abdominis has been reported to play less of a role in respiration than other abdominal muscles, such as transversus abdominis. In the present study, the inputs to transversus abdominis and rectus abdominis motoneurons were determined and compared using the transneuronal transport of two recombinant isogenic strains of pseudorabies virus. After a 5-day post-inoculation period, infected presumed motoneurons were observed principally in cord levels T10-T15 ipsilateral to the injections. The injection of a monosynaptic tracer, beta-cholera toxin, into transversus abdominis confirmed the distribution of motoneurons innervating this muscle. In the brainstem, neurons transneuronally infected following injection of pseudorabies virus into rectus abdominis or transversus abdominis were located in the same regions, which included the medial medullary reticular formation, the medullary raphe nuclei, and nucleus retroambiguus (the expiration region of the caudal ventral respiratory group). Double-labeled cells providing inputs to both rectus and transversus motoneurons were present in both the medial medullary reticular formation and nucleus retroambiguus. These data show that the medial medullary reticular formation contains neurons influencing the activity of multiple abdominal muscles, and support our hypothesis that this region globally affects the excitability of motoneurons involved in respiration.

Abdominal Muscles↗

Role of the medial medullary reticular formation in relaying vestibular signals to the diaphragm and abdominal muscles.

Changes in posture can affect the resting length of respiratory muscles, requiring alterations in the activity of these muscles if ventilation is to be unaffected. Recent studies have shown that the vestibular system contributes to altering respiratory muscle activity during movement and changes in posture. Furthermore, anatomical studies have demonstrated that many bulbospinal neurons in the medial medullary reticular formation (MRF) provide inputs to phrenic and abdominal motoneurons; because this region of the reticular formation receives substantial vestibular and other movement-related input, it seems likely that medial medullary reticulospinal neurons could adjust the activity of respiratory motoneurons during postural alterations. The objective of the present study was to determine whether functional lesions of the MRF affect inspiratory and expiratory muscle responses to activation of the vestibular system. Lidocaine or muscimol injections into the MRF produced a large increase in diaphragm and abdominal muscle responses to vestibular stimulation. These vestibulo-respiratory responses were eliminated following subsequent chemical blockade of descending pathways in the lateral medulla. However, inactivation of pathways coursing through the lateral medulla eliminated excitatory, but not inhibitory, components of vestibulo-respiratory responses. The simplest explanation for these data is that MRF neurons that receive input from the vestibular nuclei make inhibitory connections with diaphragm and abdominal motoneurons, whereas a pathway that courses laterally in the caudal medulla provides excitatory vestibular inputs to these motoneurons.

Abdominal Muscles↗

Plasma hormone levels and central c-Fos expression in ferrets after systemic administration of cholecystokinin.

Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 microg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.

Animals↗

Effects of postural changes and vestibular lesions on diaphragm and rectus abdominis activity in awake cats.

Changes in posture can affect the resting length of the diaphragm, requiring alterations in the activity of both the abdominal muscles and the diaphragm to maintain stable ventilation. To determine the role of the vestibular system in regulating respiratory muscle discharges during postural changes, spontaneous diaphragm and rectus abdominis activity and modulation of the firing of these muscles during nose-up and ear-down tilt were compared before and after removal of labyrinthine inputs in awake cats. In vestibular-intact animals, nose-up and ear-down tilts from the prone position altered rectus abdominis firing, whereas the effects of body rotation on diaphragm activity were not statistically significant. After peripheral vestibular lesions, spontaneous diaphragm and rectus abdominis discharges increased significantly (by approximately 170%), and augmentation of rectus abdominis activity during nose-up body rotation was diminished. However, spontaneous muscle activity and responses to tilt began to recover after a few days after the lesions, presumably because of plasticity in the central vestibular system. These data suggest that the vestibular system provides tonic inhibitory influences on rectus abdominis and the diaphragm and in addition contributes to eliciting increases in abdominal muscle activity during some changes in body orientation.

Abdominal Muscles↗

Angioleiomyoma: clinical presentation and surgical management.

Angioleiomyomas are relatively rare, benign, vascular soft tissue tumors with a predilection for the lower extremity. They may occur in either the cutaneous or subcutaneous tissue and are usually well encapsulated. Erosion of adjacent bone due to secondary compression phenomenon has rarely been reported in the literature. This study describes three cases.

Adult↗

Definition of neuronal circuitry controlling the activity of phrenic and abdominal motoneurons in the ferret using recombinant strains of pseudorabies virus.

During a number of behaviors, including vomiting and some postural adjustments, activity of both the diaphragm and abdominal muscles increases. Previous transneuronal tracing studies using injection of pseudorabies virus (PRV) into either the diaphragm or rectus abdominis (RA) of the ferret demonstrated that motoneurons innervating these muscles receive inputs from neurons in circumscribed regions of the spinal cord and brainstem, some of which have an overlapping distribution in the magnocellular part of the medullary reticular formation (MRF). This observation raises two possibilities: that two populations of MRF neurons provide independent inputs to inspiratory and expiratory motoneurons or that single MRF neurons have collateralized projections to both groups of motoneurons. The present study sought to distinguish between these prospects. For this purpose, recombinant isogenic strains of PRV were injected into these respiratory muscles in nine ferrets; the strain injected into the diaphragm expressed beta-galactosidase, whereas that injected into RA expressed green fluorescent protein. Immunofluorescence localization of the unique reporters of each virus revealed three populations of infected premotor neurons, two of which expressed only one virus and a third group that contained both viruses. Dual-infected neurons were predominantly located in the magnocellular part of the MRF, but were absent from both the dorsal and ventral respiratory cell groups. These data suggest that coactivation of inspiratory and expiratory muscles during behaviors such as emesis and some postural adjustments can be elicited through collateralized projections from a single group of brainstem neurons located in the MRF.

Animals↗

Adaptive plasticity in vestibular influences on cardiovascular control.

Data collected in both human subjects and animal models indicate that the vestibular system influences the control of blood pressure. In animals, peripheral vestibular lesions diminish the capacity to rapidly and accurately make cardiovascular adjustments to changes in posture. Thus, one role of vestibulo-cardiovascular influences is to elicit changes in blood distribution in the body so that stable blood pressure is maintained during movement. However, deficits in correcting blood pressure following vestibular lesions diminish over time, and are less severe when non-labyrinthine sensory cues regarding body position in space are provided. These observations show that pathways that mediate vestibulo-sympathetic reflexes can be subject to plastic changes. This review considers the adaptive plasticity in cardiovascular responses elicited by the central vestibular system. Recent data indicate that the posterior cerebellar vermis may play an important role in adaptation of these responses, such that ablation of the posterior vermis impairs recovery of orthostatic tolerance following subsequent vestibular lesions. Furthermore, recent experiments suggest that non-labyrinthine inputs to the central vestibular system may be important in controlling blood pressure during movement, particularly following vestibular dysfunction. A number of sensory inputs appear to be integrated to produce cardiovascular adjustments during changes in posture. Although loss of any one of these inputs does not induce lability in blood pressure, it is likely that maximal blood pressure stability is achieved by the integration of a variety of sensory cues signaling body position in space.

Afferent Pathways↗

Patterning of sympathetic nerve activity in response to vestibular stimulation.

Growing evidence suggests a role for the vestibular system in regulation of autonomic outflow during postural adjustments. In the present paper we review evidence for the patterning of sympathetic nerve activity elicited by vestibular stimulation. In response to electrical activation of vestibular afferents, firing of sympathetic nerves located throughout the body is altered. However, activity of the renal nerve is most sensitive to vestibular inputs. In contrast, high-intensity simultaneous activation of cutaneous and muscle inputs elicits equivalent changes in firing of the renal, superior mesenteric and lumbar colonic nerves. Responses of muscle vasoconstrictor (MVC) efferents to vestibular stimulation are either inhibitory (Type I) or are comprised of a combination of excitation and inhibition (Type II). Interestingly, single MVC units located in the hindlimb exhibited predominantly Type I responses while those located in the forelimb and face exhibited Type II responses. Furthermore, brachial and femoral arterial blood flows were dissociated in response to vestibular stimulation, such that brachial vascular resistance increased while femoral resistance decreased. These studies demonstrate that vestibulosympathetic reflexes are patterned according to both the anatomical location and innervation target of a particular sympathetic nerve, and can lead to distinct changes in local blood flow.

Animals↗

Responses of vestibular nucleus neurons to tilt following chronic bilateral removal of vestibular inputs.

Recordings were made from the vestibular nuclei of decerebrate cats that had undergone a combined bilateral labyrinthectomy and vestibular neurectomy 49-103 days previously and allowed to recover. Responses of neurons were recorded to tilts in multiple vertical planes at frequencies ranging from 0.05 to 1 Hz and amplitudes up to 15 degrees. Many spontaneously active neurons were present in the vestibular nuclei; the mean firing rate of these cells was 43 +/- 5 (SEM) spikes/s. The spontaneous firing of the neurons was irregular: the coefficient of variation was 0.86 +/- 0.14. The firing of 27% of the neurons was modulated by tilt. The plane of tilt that elicited the maximal response was typically within 25 degrees of pitch. The response gain was approximately 1 spikes/s/degree across stimulus frequencies. The response phase was near stimulus position at low frequencies, and lagged position slightly at higher frequencies (average of 35 +/- 9 degrees at 0.5 Hz). The source of the inputs eliciting modulation of vestibular nucleus activity during tilt in animals lacking vestibular inputs is unknown, but could include receptors in the trunk or limbs. These findings show that activation of vestibular nucleus neurons during vertical rotations is not exclusively the result of labyrinthine inputs, and suggest that limb and trunk inputs may play an important role in graviception and modulating vestibular-elicited reflexes.

Animals↗

Anatomic patterning in the expression of vestibulosympathetic reflexes.

To investigate the possibility that expression of vestibulosympathetic reflexes (VSR) is related to a nerve's anatomic location rather than its target organ, we compared VSR recorded from the same type of postganglionic fiber [muscle vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb, forelimb, and face. Experiments were performed on chloralose-anesthetized cats, and vestibular afferents were stimulated electrically. Single MVC unit activity was extracted by spike shape analysis of few-fiber recordings, and unit discrimination was confirmed by autocorrelation. Poststimulus time histogram analysis revealed that about half of the neurons were initially inhibited by vestibular stimulation (type 1 response), whereas the other MVC fibers were initially strongly excited (type 2 response). MVC units with types 1 and 2 responses were present in the same nerve fascicle. Barosensitivity was equivalent in the two groups, but fibers showing type 1 responses fired significantly faster than those giving type 2 responses (0.29 +/- 0.04 vs. 0.20 +/- 0.02 Hz). Nerve fibers with type 1 responses were most common in the hindlimb (21 of 29 units) and least common in the face (2 of 11 units), the difference in relative proportion being significant (P < 0.05, chi(2) test). These results support the hypothesis that VSR are anatomically patterned.

Action Potentials↗

Vestibular stimulation leads to distinct hemodynamic patterning.

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 +/- 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

Analysis of Variance↗

Transneuronal tracing of neural pathways controlling an abdominal muscle, rectus abdominis, in the ferret.

Abdominal muscles participate in generating a large number of behaviors and reflex responses, including expiration, coughing, sneezing, vomiting, postural control, production of speech, straining, facilitation of venous return to the heart, and reaction to vestibular stimulation. However, the only premotor neurons that have been conclusively shown to influence abdominal motoneurons are located in nucleus retroambiguus, the expiratory region of the caudal ventral respiratory group. In the present study, the neural circuitry controlling the activity of one abdominal muscle, rectus abdominis, was mapped using the transneuronal tracer pseudorabies virus (PRV) in the ferret. Injections of PRV into rectus abdominis labeled large presumed motoneurons in the ventral horn of T12-L4, and smaller presumed interneurons that were scattered in laminae VII, VIII, IX, and X of T4-L4. In addition, neurons in several areas of the medulla and caudal pons, including the retroambigual nucleus, medial and ventromedial reticular formation, nucleus prepositus hypoglossi, vestibular nuclei, and raphe nuclei, were infected by transynaptic passage of PRV from rectus abdominis motoneurons. Thus, the multifunctional roles of abdominal muscles appear to be coordinated by premotor neurons located in both the spinal cord and several regions of the brainstem.

Animals↗

Cardiovascular responses elicited by linear acceleration in humans.

Although activation of otolith receptors is known to elicit cardiovascular responses in animals, it is unclear whether vestibular stimulation can evoke changes in blood pressure and heart rate (which are independent of motion sickness) in humans. In the present study, ten normal subjects and three patients with profound bilateral reduction in vestibular function, who were seated upright with the torso aligned with the gravitation vector, were subjected to fore, aft, or lateral linear acceleration (approximately 0.2 g, attaining approximately 2 m/s in 900 ms, and decelerating for 3 s at 0.07 g). The head was fixed in the upright position, pitched maximally downward (chin on chest) or maximally backward (approximately 40-50 degrees) during the accelerations. In normal subjects, all directions of linear acceleration produced an average increase in systolic blood pressure of approximately 7-9 mm Hg and a rapid decrease in the interval between R-waves of the electrocardiogram of 14-27 ms; these responses persisted for only a few seconds. In contrast, the cardiovascular responses in patients with vestibular dysfunction were much smaller (e.g., the maximal pressor response to forward linear acceleration was <4 mm Hg). Head position during accelerations had little effect on the cardiovascular responses that were elicited in the population of normal subjects. However, although the population response was similar across directions of acceleration and head positions, many individuals exhibited larger cardiovascular changes during some stimulus conditions than during others. These data suggest that vestibular stimulation during linear accelerations can produce cardiovascular responses in humans and support the hypothesis that the vestibular system contributes to maintaining stable blood pressure during movement and changes in posture.

Acceleration↗

Transneuronal tracing of neural pathways controlling activity of diaphragm motoneurons in the ferret.

Previous studies have shown that neurons in addition to those in the medullary respiratory groups are involved in activating phrenic motoneurons during a number of behaviors, including vomiting and reaction to vestibular stimulation. However, the location of premotor inspiratory neurons outside of the main medullary respiratory groups is largely unknown, particularly in emetic species. In the present study, the transneuronal tracer pseudorabies virus was injected into the diaphragm of the ferret, and the locations of retrogradely-labeled motoneurons and transneuronally-labeled pre-motoneurons in the brainstem and cervical and thoracic spinal cord were mapped. Injections of a monosynaptic tracer, cholera toxin, were also made in order to verify the location of motoneurons innervating the diaphragm. Phrenic motoneurons identified with pseudorabies virus and cholera toxin were confined largely to the C5-C7 levels of spinal cord, and often gave rise to prominent polarized dendritic arbors that extended across the midline. At post-inoculation survival times > or = three days, transneuronally-labeled interneurons were located in the cervical and thoracic spinal cord and portions of the brainstem, including the midline pontomedullary reticular formation and the lateral medullary reticular formation. Double-labeling studies revealed that although the infected midline neurons were located in the proximity of serotonergic neurons, only a small number of the virus-containing cells were positive for serotonin. These findings suggest that neurons in the midline of the medulla and pons influence the activity of phrenic motoneurons, perhaps during inspiratory behaviors unique to emetic animals (such as vomiting).

Animals↗

Patterning of somatosympathetic reflexes.

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (approximately 60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (approximately 20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.

Animals↗

Effects of bilateral vestibular lesions on orthostatic tolerance in awake cats.

Previous experiments in anesthetized or decerebrate cats showed that the vestibular system participates in adjusting blood pressure during postural changes. The present experiments tested the hypothesis that removal of vestibular inputs in awake cats would affect orthostatic tolerance. Before the lesion, blood pressure typically remained within 10 mmHg of baseline values during nose-up-pitch body rotations of up to 60 degrees in amplitude. In contrast, bilateral peripheral vestibular lesions altered the pattern of orthostatic responses in all animals, and blood pressure fluctuated >10 mmHg from baseline values during most 60 degrees nose-up tilts in five of six animals. The deficit in correcting blood pressure was particularly large when the animal also was deprived of visual cues indicating position in space. During this testing condition, either a decrease or increase in blood pressure >10 mmHg in magnitude occurred in >80% of tilts. The deficit in adjusting blood pressure after vestibular lesions persisted for only 1 wk, after which time blood pressure remained stable during tilt. These data show that removal of vestibular inputs alters orthostatic responses and are consistent with the hypothesis that vestibular signals are one of several inputs that are integrated to elicit compensatory changes in blood pressure during movement.

Animals↗

Physiological basis and pharmacology of motion sickness: an update.

Motion sickness can occur when sensory inputs regarding body position in space are contradictory or are different from those predicted from experience. Signals from the vestibular system are essential for triggering motion sickness. The evolutionary significance of this malady is unclear, although it may simply represent the aberrant activation of vestibuloautonomic pathways that typically subserve homeostasis. The neural pathways that produce nausea and vomiting during motion sickness are presumed to be similar to those that generate illness after ingestion of toxins. The neural substrate of nausea is unknown but may include neurons in the hypothalamus and inferior frontal gyrus of the cerebral cortex. The principal motor act of vomiting is accomplished through the simultaneous contractions of inspiratory and expiratory respiratory muscles and is mediated by neurons in the lateral medullary reticular formation and perhaps by cells near the medullary midline. Cocontraction of the diaphragm and abdominal muscles increases pressure on the stomach, which causes gastric contents to be ejected through the mouth. Effective drugs for combating motion sickness include antihistamines, antimuscarinics, 5-HT1A (serotonergic) receptor agonists and neurokinin type 1 receptor antagonists. However, considerable information concerning the physiological basis and pharmacology of motion sickness is unknown; future research using animal models will be required to understand this condition.

Antiemetics↗