Skip to main content


URMC / Labs / Holt Lab

Synaptic Pharmacology of the Vestibular Apparatus

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 whose output then modifies subsequent information coming 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 these efferent loops is presumably to optimize or tune each sensory modality to its stimulus. Additionally, these efferent pathways may also provide the appropriate circuitry for interactions with other sensory systems.

Sensory information regarding the position and movement of the head are encoded by the vestibular system, which begins as a number of small detectors called hair cells 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, this lab is addressing the function of the vestibular efferent system from four vantage points:

  1. Identifying the receptor mechanisms by which different efferent responses are generated during activation of their pathways;
  2. Characterizing how these efferent receptor mechanisms modulate afferent response properties by pairing afferent recordings during vestibular stimulation with activation of efferent pathways;
  3. Identification of efferent discharge patterns with direct, in vivo recordings from vestibular efferent neurons.
  4. Development of behavioral assays for monitoring and evaluating vestibular efferent function in alert animal models.

Individuals working in the lab can expect to learn neurophysiological, pharmacological, and immunohistochemical methods for studying vestibular synaptic transmission in several animal models, and the necessary computational techniques for analyzing these data.