Our long-term goal is to understand the cellular mechanisms determining the discharge properties of vestibular-nerve afferents. To this end, an in vitro preparation of the turtle posterior crista has been developed. Its advantages are: 1) Afferent discharge properties are indistinguishable in the in vitro preparation and in intact, respiring animals. 2) Type I hair cells are restricted to a central zone, they make up the large majority of hair cells in this zone, and they are innervated by afferents having distinctive physiological properties. In a similar vein, bouton afferents differing in their physiological properties innervate distinct parts of the peripheral zone. Hence, by studying hair cells harvested from the different regions, it should be possible to correlate the physiology of hair cells and of the afferents innervating them. 3) Electrical stimulation of efferents produces excitation in some afferents and inhibition in others. Since the two kinds of afferents innervate distinct parts of the neuroepithelium, a study of hair cells drawn from specific regions should allow us to determine the cellular basis for both kinds of efferent actions. 4) Hair cells from this organ are relatively easy to isolate and to characterize with whole-cell tight-seal recordings. There are three specific aims: 1) To complete studies of vestibular- nerve discharge in the in vitro preparation. Afferents are characterized in terms of their responses to head rotations, their responses to electrical stimulation of efferent fibers, and the location and morphology of their peripheral terminations. 2) To characterize type I and type II hair cells, isolated from specific regions of the neuroepithelium, in terms of their voltage- and ion-sensitive currents, as well as the current evoked by the efferent transmitter, acetylcholine (ACh). 3) To extend the studies to the utricular macula of the turtle because this end organ offers advantages for some of the research planned for the next several years. The proposed studies are intended to contribute to two questions. What are the distinctive functions of type I hair cells and their calyx endings? What is the function of the efferent regulation of the vestibular end organs? The questions are of importance in understanding the operation of the vestibular labyrinth in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC002058-01
Application #
3218582
Study Section
Hearing Research Study Section (HAR)
Project Start
1993-07-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Contini, Donatella; Price, Steven D; Art, Jonathan J (2017) Accumulation of K+ in the synaptic cleft modulates activity by influencing both vestibular hair cell and calyx afferent in the turtle. J Physiol 595:777-803
Holt, J Chris; Jordan, Paivi M; Lysakowski, Anna et al. (2017) Muscarinic Acetylcholine Receptors and M-Currents Underlie Efferent-Mediated Slow Excitation in Calyx-Bearing Vestibular Afferents. J Neurosci 37:1873-1887
Liu, Xiao-Ping; Wooltorton, Julian R A; Gaboyard-Niay, Sophie et al. (2016) Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents. J Neurophysiol 115:2536-55
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

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