This is a continuing study of synaptic transmission in vestibular organs with emphasis on the type I hair cell and its calyx ending, phylogenetically recent acquisitions only found in reptiles, birds and mammals. These structures are restricted to central/striolar zones in reptiles and birds. Their increasing importance in mammals is suggested by their distribution throughout the neuroepithelium of all organs. In addition, while type I and type II hair cells occur in approximately equal numbers in rodent cristae, type I hair cells predominate in the cristae of monkeys and possibly of humans. The peculiar structure and distinctive physiology of these structures raise problems as to how synaptic transmission is accomplished. 1) Type I hair cells have a distinctive basolateral current that may compromise synaptic transmission;2) Housekeeping functions cannot be done by supporting cells;and 3) The geometry and electrophysiology of the calyx ending place unusual demands on the flow of synaptic currents to the spike encoder. We have only fragmentary knowledge as to how these problems are solved. Yet, because these structures become of increasing importance in mammals (including humans), such knowledge is crucial to our understanding as to how vestibular organs process information. Of clinical interest, the type I hair cell and/or its calyx ending are especially sensitive to aminoglycoside ototoxicity and age-related degeneration. Physiological studies will be done in the turtle posterior crista and will be integrated with morphological studies to be done in rats and turtles. There are three specific aims. 1) Hair cells: We will characterize synaptic transmission from type I hair cells by making whole- cell recordings from the calyx ending. The hypothesis is that neurotransmitter release from type I hair in low- frequency vestibular hair cells may differ from high-frequency auditory and vibratory organs. 2) Homeostasis: Both K+ ions and glutamate neurotransmitter are released from hair cells during transduction. In the case of type II hair cells, supporting cells serve to clear these substances. The presence of the calyx ending precludes supporting cells from acting in the same way for type I hair cells. We hypothesize that the type I hair cell and/or its ending subsume these housekeeping functions. 3) Postsynaptic mechanisms: We will explore how various ion channels and neurotransmitter receptors shape synaptic and spiking activity. The hypothesis to be tested is that the molecular organization of the calyx creates separate microdomains with discrete functions: synaptic transmission, spike initiation, and discharge regularity.

Public Health Relevance

Because type I hair cells and their calyx endings become of increasing importance in mammals (including humans), such knowledge is crucial to our understanding as to how vestibular organs process information. Of clinical interest, the type I hair cell and/or its calyx ending may be especially sensitive to aminoglycoside ototoxicity and age-related degeneration.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Auditory System Study Section (AUD)
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Cyr, Janet
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University of Chicago
Schools of Medicine
United States
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Contini, Donatella; Price, Steven D; Art, Jonathan J (2016) Accumulation of K(+) in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle. J Physiol :
Gatto, Rodolfo G; Chu, Yaping; Ye, Allen Q et al. (2015) Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington's disease. Hum Mol Genet 24:5285-98
Holt, J Chris; Kewin, Kevin; Jordan, Paivi M et al. (2015) Pharmacologically distinct nicotinic acetylcholine receptors drive efferent-mediated excitation in calyx-bearing vestibular afferents. J Neurosci 35:3625-43
Goldberg, Jay M; Holt, Joseph C (2013) Discharge regularity in the turtle posterior crista: comparisons between experiment and theory. J Neurophysiol 110:2830-48
Dalet, Antoine; Bonsacquet, Jeremie; Gaboyard-Niay, Sophie et al. (2012) Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings. PLoS One 7:e46261
Schraven, Sebastian P; Franz, Christoph; Ruttiger, Lukas et al. (2012) Altered phenotype of the vestibular organ in GLAST-1 null mice. J Assoc Res Otolaryngol 13:323-33
Lysakowski, Anna; Gaboyard-Niay, Sophie; Calin-Jageman, Irina et al. (2011) Molecular microdomains in a sensory terminal, the vestibular calyx ending. J Neurosci 31:10101-14
Goldberg, Jay M; Cullen, Kathleen E (2011) Vestibular control of the head: possible functions of the vestibulocollic reflex. Exp Brain Res 210:331-45
Lysakowski, Anna; Goldberg, Jay M (2008) Ultrastructural analysis of the cristae ampullares in the squirrel monkey (Saimiri sciureus). J Comp Neurol 511:47-64
Holt, Joseph C; Chatlani, Shilpa; Lysakowski, Anna et al. (2007) Quantal and nonquantal transmission in calyx-bearing fibers of the turtle posterior crista. J Neurophysiol 98:1083-101

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