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Biomedical subjects

B J Yates

Publications and source records attributed to B J Yates.

At least 55 records · Page 3Linked to original sources

Influences of neck afferents on sympathetic and respiratory nerve activity.

It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue musculature are complementary, presumably to produce tongue protrusion either during movements of the head alone or of the whole body.

Afferent Pathways↗

Integration of somatic and visceral inputs by the brainstem: functional considerations.

Studies of the brainstem have traditionally either focused on mechanisms for the control of limb or axial muscles or for the maintenance of homeostasis (e.g., the circuitry for the regulation of respiration or blood pressure). However, recent studies have demonstrated that movement and changes in cardiorespiratory activity often are coordinated, indicating a linkage between the pathways that control somatic motor activity and those that regulate respiration or circulation. Neurons in regions such as nucleus tractus solitarius and the lateral medullary reticular formation that regulate circulation and respiration have been shown to receive somatic sensory signals (including those from the vestibular system) indicating body position in space. In addition, somatic motor control may be influenced by signals from visceral receptors that provide cues regarding body position in space. Some areas of the brainstem may also participate directly in both motor control and regulation of blood pressure and respiration. Thus, a simple division of the brainstem into "somatic" and "autonomic" regions is no longer possible.

Afferent Pathways↗

Post-spaceflight orthostatic intolerance: possible relationship to microgravity-induced plasticity in the vestibular system.

Even after short spaceflights, most astronauts experience at least some postflight reduction of orthostatic tolerance; this problem is severe in some subjects. The mechanisms leading to postflight orthostatic intolerance are not well-established, but have traditionally been thought to include the following: changes in leg hemodynamics, alterations in baroreceptor reflex gain, decreases in exercise tolerance and aerobic fitness, hypovolemia, and altered sensitivity of beta-adrenergic receptors in the periphery. Recent studies have demonstrated that signals from vestibular otolith organs play an important role in regulating blood pressure during changes in posture in a 1-g environment. Because spaceflight results in plastic changes in the vestibular otolith organs and in the processing of inputs from otolith receptors, it is possible that another contributing factor to postflight orthostatic hypotension is alterations in the gain of vestibular influences on cardiovascular control. Preliminary data support this hypothesis, although controlled studies will be required to determine the relationship between changes in the vestibular system and orthostatic hypotension following exposure to microgravity.

Humans↗

Autonomic reaction to vestibular damage.

The vestibular system provides inputs to many neurons in the brain stem that participate in autonomic control. This multiplicity of vestibular-autonomic connections plays a variety of roles. Whereas it has been known for decades that unilateral vestibular lesions can result in motion sickness, recent data suggest that the vestibular system participates in making adjustments in blood pressure and respiration that are necessary to maintain homeostasis during movement and changes in posture. Animals with bilateral vestibular lesions are more susceptible to posturally related hypotension than vestibularly intact animals, and it is also possible that orthostatic hypotension after space flight is caused in part by microgravity-related changes in otolith function. Patients with vestibular lesions could also be more vulnerable to respiratory disturbances related to posture, such as obstructive apnea. Vestibular dysfunction has additionally been linked with anxiety disorders, such as agoraphobia, which may result from alteration of vestibular inputs to brain stem monoaminergic neurons (which are known to process these signals). Even sleep disturbances might be connected with vestibular disorders because neurons in the pontine reticular formation that are critical in switching between sleep states may be influenced by labyrinthine inputs. Thus it is likely that vestibular damage will result in a number of parallel disturbances in autonomic function.

Animals↗

Regional and functional differences in the distribution of vestibulosympathetic reflexes.

Although considerable evidence suggests that the vestibular system regulates sympathetic outflow during movement and changes in posture, little is known about relative vestibular influences on activity of different sympathetic nerves and sympathetic efferents with different functions. In the present study, we demonstrated that electrical stimulation of the vestibular nerve in the cat elicited responses in sympathetic nerves innervating the head and abdominal viscera. This observation suggests that activity of sympathetic efferents innervating multiple body regions is affected by vestibular signals. These responses were attenuated by >80% when blood pressure was increased to >160 mmHg. Because raising blood pressure decreases the responsiveness of vasoconstrictor fibers, the simplest explanation for these data is that the vestibular system provides particularly strong inputs to components of the sympathetic nervous system that regulate peripheral vascular resistance. Furthermore, the relative magnitude of vestibulosympathetic reflexes was over four times larger in one sympathetic nerve composed mainly of vasoconstrictor efferents (renal nerve) than another nerve (external carotid nerve) containing similar types of fibers. Collectively, these data indicate that the vestibular system has selective influences on sympathetic outflow to particular tissues and body regions.

Animals↗

Vestibular influences on cat lumbar paravertebral muscles.

Recordings were made from nerves innervating ventral lumbar paravertebral muscles (quadratus lumborum) during natural vestibular stimulation in vertical planes. The best direction of vestibular stimulation for producing an increase in nerve activity was near nose-up pitch in two-thirds of the animals, but was near nose-down pitch in the others. The response gain (re. position) was flat across the frequency range of 0.05-1 Hz, and the responses persisted throughout 11-s static tilts. These data suggest that otolith organs activated by pitch influence activity in the lumbar paravertebral muscles. These responses may serve to stabilize the vertebral column during movements involving body pitch, such as vertical climbing.

Animals↗

Pressor response elicited by nose-up vestibular stimulation in cats.

The purpose of the present study was to determine whether selective activation of vestibular receptors produces changes in blood pressure. Blood pressure was recorded during trapezoidal head rotations in cats with extensive denervations to eliminate nonlabyrinthine inputs that could be produced by the movements. Large (50 degrees) nose-up trapezoidal head tilts produced an increase in blood pressure of approximately 18 mmHg; ear-down tilt produced little change in blood pressure. The changes in blood pressure began approximately 1.4 s after the plateau of the stimulus. The responses to nose-up tilt were abolished following intracranial transections of the VIIIth cranial nerves. These data suggest that vestibular inputs elicited by nose-up movements of the head act to rapidly increase blood pressure. This mechanism may contribute to counteracting the orthostatic hypotension induced by nose-up body rotation in quadrupeds.

Abducens Nerve↗

Connections of the caudal ventrolateral medullary reticular formation in the cat brainstem.

A region of the caudal ventrolateral medullary reticular formation (CVLM) participates in baroreceptor, vestibulosympathetic, and somatosympathetic reflexes; the adjacent retroambigual area is involved in generating respiratory-related activity and is essential for control of the upper airway during vocalization. However, little is known about the connections of the CVLM in the cat. In order to determine the locations of terminations of CVLM neurons, the anterograde tracers Phaseolus vulgaris leucoagglutinin and tetramethylrhodamine dextran amine were injected into this region. These injections produced a dense concentration of labeled axons throughout the lateral medullary reticular formation (lateral tegmental field), including the retrofacial nucleus and nucleus ambiguus, regions of the rostral ventrolateral medulla, the lateral and ventrolateral aspects of the hypoglossal nucleus, nucleus intercalatus, and the facial nucleus. A smaller number of labeled axons were located in the medial, lateral, and commissural subnuclei of nucleus tractus solitarius, the A5 region of the pontine reticular formation, the ventral and medial portions of the spinal and motor trigeminal nuclei, locus coeruleus, and the parabrachial nucleus. We confirmed the projection from the CVLM to both the rostral ventrolateral medulla and lateral tegmental field using retrograde tracing. Injections of biotinylated dextran amine or Fluorogold into these regions resulted in retrogradely labeled cell bodies in the CVLM. However, the neurons projecting to the lateral tegmental field were located mainly dorsal to those projecting to the rostral ventrolateral medulla, suggesting that these neurons form two groups, possibly with different inputs. Injections of retrograde tracers into the lateral tegmental field and rostral ventrolateral medulla also produced labeled cell bodies in other regions, including the medial and inferior vestibular nuclei and nucleus solitarius. These data are consistent with the view that the CVLM of the cat is a multifunctional area that regulates blood pressure, produces vocalization, affects the shape of the oral cavity, and elicits contraction of particular facial muscles.

Animals↗

Responses of ventral respiratory group neurons of the cat to natural vestibular stimulation.

Stimulation of vestibular otolith afferents by fore-aft tilt (pitch) elicits changes in activity of nerves innervating respiratory muscles, including the diaphragm, abdominal muscles, and tongue musculature. To determine the role of ventral respiratory group (VRG) neurons in producing these vestibular-respiratory responses, the activity of VRG neurons was recorded during natural vestibular stimulation in multiple transverse planes. Only a small fraction of VRG neurons with inspiratory (I, 20 of 80 cells), expiratory (E, 11 of 59 cells), or phase spanning (4 of 16 cells) activity responded to tilts up to 15 degrees in amplitude delivered at frequencies from 0.02 to 2 Hz. In particular, responses were infrequent in VRG neurons with projections to the spinal cord (0 of 23 E cells and 2 of 15 degrees I cells), despite the fact that the tilts employed produced robust modulation of the activity of abdominal (expiratory) nerves. Furthermore, the characteristics of responses to tilt of the small fraction of VRG neurons with vestibular inputs did not match those of respiratory muscles. These data suggest that neurons in addition to those in the VRG must participate in generating vestibular-respiratory responses.

Abdominal Muscles↗

Differential tropism of pseudorabies virus for sensory neurons in the cat.

The permissiveness of cat motor and sensory systems to infection by pseudorabies virus (PRV) was examined. Eight adult cats of both sexes received injections of a virulent strain of PRV (PRV-Becker) into either the diaphragm or neck musculature. Temporal analysis of the replication and transynaptic passage of virus in each experimental paradigm revealed that sensory neurons in the dorsal root ganglia were more susceptible to infection than motor neurons. Only scattered motor neurons displayed productive replication of virus at postinoculation intervals extending to 192 h whereas robust replication of virus in neurons in the dorsal root ganglia and dorsal horn of the spinal cord was apparent as early as 96 h post inoculation. The data demonstrate that functionally distinct populations of neurons in the cat are differentially permissive to infection and transneuronal transport of PRV.

Animals↗

Modulation of vomiting by the medullary midline.

Studies were conducted to investigate the possible role of the brainstem midline region as a source of facilitatory input for the vomiting process. Experiments were conducted using the "fictive vomiting' model in decerebrate, paralysed cats. Dysfunction of the medullary midline region produced by localized injections of the neurotoxin kainic acid abolished or greatly attenuated fictive vomiting. In addition, some respiratory-related midline neurons were found to fire in synchrony with co-active phrenic and abdominal nerve discharge during fictive vomiting. These experiments demonstrate the importance of the medullary midline for the normal occurrence of the vomiting process. An explanation for the post-lesion elimination of vomiting is that the lesions remove an important source of facilitatory input to spinal respiratory motoneurons and/or to the brainstem circuitry that mediates vomiting.

Animals↗

Vestibular influences on the autonomic nervous system.

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.

Animals↗

Vestibular influences on hypoglossal nerve activity in the cat.

The purpose of the present study was to determine if selective activation of vestibular receptors during movement produces changes in hypoglossal nerve activity. Responses were recorded from the hypoglossal nerves during trapezoidal and sinusoidal head rotations in cats with extensive denervations to eliminate non-labyrinthine inputs that could be produced by the movements. Large (50 degrees) nose-up trapezoidal tilts produced an increase in nerve discharge; ear-down tilt was also effective in one-fourth of the animals. The responses to nose-up tilt were abolished following intracranial transections of the VIIIth cranial nerves. Smaller (20 degrees) sinusoidal head rotations in the roll, pitch and yaw planes were ineffective in producing responses. These data suggest that vestibular inputs elicited by nose-up pitch contribute to tongue protrusion and participate in maintaining airway patency by preventing the tongue from falling to the back of the mouth.

Animals↗

Brainstem interneurons necessary for vestibular influences on sympathetic outflow.

The objective of this study was to determine which general brainstem regions contain interneurons that are critical for mediating vestibulo-sympathetic responses in decerebrate cats, as a prelude for future cell recording studies. Large injections of kainic acid into the lateral reticular formation at levels caudal to the obex abolished sympathetic nerve responses elicited by electrical stimulation of the vestibular nerve. The same lesions also diminished excitatory and some inhibitory components of somato-sympathetic responses elicited by stimulation of the sciatic nerve, raising the possibility that a common pool of interneurons integrates signals from muscle, skin and the vestibular system that reflect body position in space. Large lesions of other brainstem regions containing interneurons involved in regulation of sympathetic activity, including nucleus tractus solitarius, the lateral tegmental field rostral to the obex, and the parabrachial nucleus, had no appreciable effect on the amplitude of either vestibulo-sympathetic or somato-sympathetic responses. Thus, interneurons critical for relaying vestibular and other somatic signals to descending cardiovascular-regulatory pathways appear to be located in the caudal and lateral parts of the medulla.

Animals↗

Processing of vestibular and other inputs by the caudal ventrolateral medullary reticular formation.

Lesions of the lateral medullary reticular formation caudal to the obex abolish vestibulosympathetic and somatosympathetic responses; this area also contains neurons that mediate baroreceptor reflexes. Recordings were made from neurons in the caudal medullary reticular formation of cats that were decerebrate or anesthetized using alpha-chloralose-urethan to determine whether common neurons responded to electrical stimulation of vestibular and hindlimb afferents and had cardiac-related (i.e., baroreceptor) inputs. Many neurons in the ventrolateral portion of the caudal reticular formation received labyrinthine inputs, and they were interspersed with neurons that received baroreceptor signals. However, virtually none of the units received convergent baroreceptor and vestibular inputs, suggesting that separate pathways from the caudal ventrolateral medulla mediate baroreceptor and vestibulosympathetic reflexes. Furthermore, the neurons that received labyrinthine signals could not be antidromically activated from electrodes inserted into the rostral ventrolateral medulla, which is known to mediate vestibulosympathetic responses; thus an indirect pathway must convey vestibular inputs from the caudal to rostral medullary reticular formation. Over 75% of both neurons with baroreceptor inputs and cells with vestibular signals responded to sciatic nerve stimulation, suggesting that more than one pathway from the caudal medulla may mediate somatosympathetic responses.

Afferent Pathways↗

Changes in outflow to respiratory pump muscles produced by natural vestibular stimulation.

1. Activity was recorded from abdominal (expiratory) and phrenic (inspiratory) nerves during natural vestibular stimulation in multiple vertical planes and the horizontal plane in decerebrate cats. Vestibular stimulation was produced by rotating the head in animals whose upper cervical dorsal roots were transected to remove inputs from neck receptors; the upper airway and carotid sinus were denervated, and the vagus nerves were transected to assure that the head rotations did not elicit visceral or pulmonary inputs. 2. The plane of head rotation that produced maximal modulation of respiratory nerve activity (response vector orientation) was measured at one or more frequencies between 0.05 and 0.5 Hz. The dynamics of the response were then studied with sinusoidal (0.05-2 Hz) stimuli aligned with this orientation. In some animals, sinusoidal horizontal rotations of the head at 0.5 and 1 Hz or static head tilts in the pitch and roll planes were also delivered. 3. Typically, maximal modulation of abdominal nerve outflow was elicited by head rotations in a plane near pitch; nose-up rotations produced increased outflow, and nose-down rotations reduced nerve discharges. The gains of the responses (relative to stimulus position) remained relatively constant across stimulus frequencies, and the phases were consistently near stimulus position, like regularly firing otolith afferents. Static nose-up tilt produced elevated abdominal nerve activity throughout the stimulus period, providing further evidence that pitch-sensitive otolith receptors contribute to the response. Horizontal head rotations had little influence on abdominal nerve discharges. 4. The abdominal nerve responses to head rotation were abolished by chemical or aspiration lesions of the medial and inferior vestibular nuclei, which is concordant with the responses resulting from activation of vestibular receptors. Transections of axons arising from bulbospinal neurons in the ventral respiratory group, which are known to be the predominant source of expiratory signals to the spinal cord, reduced but did not abolish the vestibuloabdominal reflex. Thus it is likely that nonrespiratory neurons also participate in generating this response. 5. Nose-up pitch of the head; and in particular large (50 degrees) static tilts, produced small increases in phrenic nerve activity. Ear-down tilt and horizontal rotation of the head produced no responses in the phrenic nerve. 6. The existence of vestibular inputs to some respiratory motoneurons suggests that the vestibular system has influences on muscles in addition to those typically considered to have antigravity roles, and participates globally in adjusting muscle activity during movement and changes in posture.

Animals↗

Vestibular inputs to the lateral tegmental field of the cat: potential role in autonomic control.

The lateral tegmental field (LTF), which is comprised of the lateral reticular formation near the obex, is an important integrative area involved in cardiovascular control and the production of emesis. Using neuroanatomical and electrophysiological techniques, we tested the hypothesis that LTF neurons receive vestibular inputs; the neurons studied included those projecting into the subretrofacial rostral ventrolateral medulla (sRVLM), which contains cells that make direct connections with sympathetic preganglionic neurons. Injections of the anterograde tracer PHA-L into the medial and inferior vestibular nuclei produced labeled terminals in the LTF. Electrical stimulation of the vestibular nerve affected the firing rate of LTF neurons, including approximately one-third of those antidromically activated from the sRVLM. The response latencies ranged from 1.5 to 20 ms, suggesting that the neurons received both direct and polysynaptic vestibular inputs from the vestibular nuclei. The LTF may be involved in the production of vestibulosympathetic reflexes and vestibular-elicited vomiting.

Animals↗