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Cellular and Molecular Mechanisms of Synaptic Transmission in the Vestibular Periphery
Many sensory systems are endowed with efferent feedback mechanisms that can modulate their primary input to the brain. That is, incoming information from a peripheral detector is delivered to a way station within the CNS which then modifies the output from that same detector. Everyday examples include the pupillary reflex to bright light entering the eyes, the contraction of middle ear muscles to loud sounds, or the recruitment of additional muscle fibers when first lifting a heavy object. Here, the function of the efferent loop is presumably to optimize or tune each sensory modality to its stimulus. Sensory information regarding the position and movement of the head are encoded by the vestibular system, which begins as a number of small detectors located within the inner ear.
Like the preceding examples, the peripheral vestibular system is also endowed with a prominent efferent innervation. The functional role of this feedback system, however, is relatively unknown. We do know that when these efferent pathways are electrically stimulated, afferent output from vestibular endorgans is profoundly inhibited or excited, suggesting that vestibular efferents may be involved in both negative and positive feedback. If such efferent activity occurs under physiological conditions, it is almost certain to modify and transform vestibular information traveling to the CNS. Yet, very little information is available as to how and when these efferent actions ultimately impact the processing of vestibular information in an alert animal.
Taking a reductionistic approach, my lab is addressing the function of the vestibular efferent system from three vantage points:
- Identifying the receptor mechanisms by which different efferent responses are generated during activation of their pathways;
- Characterizing how these efferent receptor mechanisms modulate afferent response properties by pairing afferent recordings during vestibular stimulation with activation of efferent pathways; and
- Identification of efferent discharge patterns with direct, in vivo recordings from vestibular efferent neurons.
Such knowledge is critical in evaluating efferent function in behaving animal models, one of our long term goals. Students rotating in the lab can learn neurophysiological, pharmacological, and immunohistochemical methods for studying vestibular synaptic transmission in several animal models, and the necessary computational techniques for analyzing these data.
For specific questions, please contact Prof. Holt