The long-term goal of this work is to understand how vestibular organs work. The proper function of these organs is crucial to a healthy existence; damage can lead to debilitating vertigo, dizziness and inability to maintain study gaze. Mamammal, birds and reptiles have similar vestibular organs, with two classes of sensory receptor cell, the type I and type II hair cells. These cells transduce head movements into electrochemical signals that are transmitted across synapses to the terminals of afferent nerve fibers, which convey the signals to the brain in the form of electrical discharges. Efferent nerve fibers from the brain make synapses on h air cells and afferent nerve terminals, through which they influence afferent signals by unknown mechanisms.
The specific aims are to characterize: 1) afferent synaptic transmission from the hair cells to the neurons; 2) the cellular mechanisms responsible for discharge regularity and maximum evoked discharge rates of afferent neurons; 3) efferent actions. In vitro preparations of the posterior semicircular canal organ of the turtle will be used. This organ lends itself to comparison of type I and type II hair cells, shows richly diverse efferent actions on afferent nerve fiber discharges, and is robust in vitro. Depending on the specific experiment, stimuli will be mechanical (displacement of the canal fluid), manipulations of membrane voltage or current in hair cells or afferent neurons, or electrical stimulation of efferent nerve fibers. The membrane voltage or current responses of hair cells and afferent neurons to these stimuli will be recorded intra cellularly with sharp micropipettes or patch pipettes. Both conventional (vesicular, orthograde) and unusual forms of transmission between the type I hair cell and afferent neuron will be characterized. Whether afferent discharge regularity is due to presynaptic (hair cell) or postsynaptic (afferent neuron) mechanisms will be tested. whether stages following mechanoelectrical traduction determine saturation of afferent discharge rates will be investigated. Efferent-evoked synaptic potentials and the neurotransmitter receptors responsible will be characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002058-05
Application #
2733673
Study Section
Hearing Research Study Section (HAR)
Project Start
1993-07-01
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Chicago
Department
Neurology
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

Showing the most recent 10 out of 23 publications