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Dr. Yates' CV is available for download as PDF

Research Interests

Vestibular Influences on Autonomic Control

Problem:
A key role of the central nervous system is to provide for homeostasis, or a stable internal milieu. One of the most profound challenges to homeostasis occurs when a human or other animal moves or changes posture. In particular, some movements, such as standing in humans or nose-up body pitch in quadrupeds, can threaten the maintenance of stable blood pressure and blood oxygenation. Unless compensation takes place quickly, these movements produce (1) blood pooling in the lower body that results in orthostatic hypotension and (2) a change in the resting length of the respiratory muscles that results in decreased air flow through the lungs. Many body sensors, including arterial baroreceptors, receptors in the heart, receptors in limb veins, receptors in the lungs, stretch receptors in respiratory muscles, and central and peripheral chemoreceptors, detect disturbances in homeostasis and trigger appropriate compensatory responses. However, effective maintenance of homeostasis would seem to require that compensation for the effects of movement on circulation and respiration begin even before the internal environment has been affected. One mechanism for accomplishing this would be through the actions of the vestibular system, which detects head position and head movements, and could thus provide "feed-forward" information to the brainstem autonomic centers, resulting in corrections in blood pressure and ventilation during changes in body position. The major research in our laboratory looks at the role of the vestibular system in adjusting blood pressure and respiration during movement and changes in posture. We are also determining the neural pathways through which vestibular signals influence the sympathetic nervous system (which controls blood pressure) and respiratory motoneurons. Finally, we are interested in determining which neural pathways are responsible for producing an aberrant autonomic effect that can result from vestibular stimulation: motion sickness.

Techniques:
This research involves many different techniques. In looking at the physiological role of vestibular influences on respiration and circulation, our research makes use of recordings of blood pressure, blood flow, blood catecholamine levels, activity of sympathetic and respiratory nerves, and activity of respiratory muscles. When determining the neural pathways that are responsible for mediating vestibular influences on respiration and circulation and for producing motion sickness, we use conventional and transneuronal neuroanatomical techniques as well as single-unit in vivo recordings. Our laboratory has a unique complement of devices for producing natural vestibular stimulation in 3 dimensions, which allows for sophisticated studies of vestibular processing.

Our facilities permit studies on a variety of animal species, and allow the use of anesthetized, decerebrate and chronic preparations.

Significance:
This research has a number of important practical implications. The fact that vestibular stimulation has autonomic effects is of relevance to all vestibular researchers. Autonomic effects of vestibular stimulation, or changes in autonomic functioning resulting from vestibular lesions, can indirectly have effects on other vestibular reflexes. For example, fluid loss associated with vestibular-induced emesis or orthostatic hypotension resulting from vestibular lesions could result in lightheadedness during rapid and unexpected changes in posture. This lightheadedness could indirectly have effects of vestibulo-spinal and vestibulo-ocular reflexes. Furthermore, motion sickness and dysfunction in vestibular autonomic regulation can result in distress and reduced attention to environmental stimuli, and thereby alter other vestibular reflexes.

Connections between the vestibular system and brainstem autonomic centers can also be important in clinical medicine. As discussed above, vestibular lesions can increase the susceptibility for orthostatic hypotension and may decrease the ability to rapidly adjust respiration during movement. Neuroanatomical studies showing direct connections between the vestibular nuclei, the locus coeruleus, and brainstem pathways that process visceral sensory information also provide a potential neural substrate for the autonomic and affective signs and symptoms often associated with vestibular dysfunction. Clinical studies have shown a close linkage between generalized anxiety, panic disorder, agoraphobia and vestibular dysfunction. Common to patients with panic disorder and agoraphobia are heightened sensations of discomfort with motion and with changes in body position in space. Thus, alterations in vestibular functioning may contribute to some psychiatric disorders.

Vestibular autonomic regulation also has important implications for the space life sciences. Substantial data already indicate that vestibular-autonomic pathways are at least partially responsible for space motion sickness, and plastic changes in the vestibular system during space flight also may be partially responsible for postflight orthostatic intolerance. Other physiological problems experienced by astronauts, including sleep disturbances, could additionally be linked with microgravity-related changes in the vestibular system. Further research is required to determine the relationship between changes in vestibular functioning and alterations in a number of physiological processes during and subsequent to spaceflight.

With the longer duration space flights planned for the future, including the International Space Station assignments of 90-180 days and missions to Mars, which may require three years, vestibular-autonomic disturbances may become of even greater significance to NASA. A Mars mission will be further complicated by the requirement for crew members to egress in the partial-gravity environment of Mars without assistance after a flight of many months. Thus, it is imperative that we better understand the implications of changes in vestibular autonomic regulation during space flight, and that we develop countermeasures to prevent or compensate for these changes.

The Role of the Vestibular System in Spatial Cognition

Navigation requires two types of information: knowledge of directional heading and place in the environment. Neurons located in several regions of the central nervous system, called head direction cells, are believed to provide the neural substrate for directional heading. Furthermore, research in the laboratory of Dr. Jeff Taube at Dartmouth University has suggested that the vestibular system plays a critical role in shaping the discharge properties of head direction cells. We are currently employing neurophysiological and neuroanatomical approaches to determine the role that the vestibular system plays in spatial cognition, and are also mapping the neural pathways that relay vestibular signals to brain regions that contain head direction cells.

Monoaminergic Influences on Vestibular Reflexes

Monoaminergic transmitters (including serotonin and norepinephrine) produce long-lasting influences on their targets, which include neurons in the brainstem and spinal cord that receive vestibular signals (e.g., cells in the vestibular nuclei, reticular formation, intermediolateral and ventral horns of the spinal cord). Furthermore, brainstem neurons that synthesize monoaminergic transmitters, including those in nucleus locus coeruleus and the raphe nuclei, receive vestibular signals. Another line of research in our laboratory examines the role of monaminergic neurons in modulating vestibulo-spinal reflexes acting on the limbs, vestibulo-sympathetic reflexes, and vestibulo-respiratory responses. As with our research on vestibular influences on autonomic functions, these experiments involve both neuroanatomical and physiological approaches. In combination, these experiments will reveal the role of monoaminergic neurons in "shaping" the properties of vestibulo-spinal, vestibulo-sympathetic, and vestibulo-respiratory responses.

"Science is simply common sense at its best that is, rigidly accurate in observation, and merciless to fallacy in logic."

Thomas Henry Huxley (1825-95) English biologist.