Principal Investigator

Joseph Christopher Holt, Ph.D. University of Rochester work Box 629 601 Elmwood Ave Rochester NY 14642 office: MC 6-8549 p (585) 273-3064 f (585) 756-5334

Contact

Holt Lab University of Rochester work MC 6-7556 601 Elmwood Ave Rochester NY 14642 p (585) 276-2703 f (585) 756-5334

Affiliations

Synaptic Pharmacology of the Vestibular Apparatus

Vestibular hair cells and afferents (green) are heavily innervated by efferent neurons (red).

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.

Vestibular efferent circuitry

Vestibular efferent circuitry in the periphery and central nervous system. Efferent neurons originate in the brainstem in nuclei called E-Group. From there, they send axons that travel in cranial nerve VIII and then extensively branch and terminate in the neuroepithelium of the vestibular endorgans. Upon termination, efferent neurons synapse on type II hair cells, bouton afferents innervating type II hair cells, and on the calyx endings innervating type I hair cells. The appropriate vestibular stimulus is detected by the apical hair cell bundle which is then transduced into a electrochemical signal at the hair cell – afferent synapse. Action potentials in the afferent neurons are relayed to the vestibular nuclei (VN) and higher CNS centers. Information from the VN may be routed to the reticular formation which is thought to be one of the main areas projecting to E-group. Non-vestibular input (e.g. other sensory systems) may also use the reticular formation and E-group to interact with the vestibular periphery.

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.