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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002058-17
Application #
8508905
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
1993-07-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
17
Fiscal Year
2013
Total Cost
$299,326
Indirect Cost
$53,294
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
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
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
Holt, Joseph C; Lysakowski, Anna; Goldberg, Jay M (2006) Mechanisms of efferent-mediated responses in the turtle posterior crista. J Neurosci 26:13180-93
Bao, Hong; Wong, Weng Hoe; Goldberg, Jay M et al. (2003) Voltage-gated calcium channel currents in type I and type II hair cells isolated from the rat crista. J Neurophysiol 90:155-64
Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne et al. (2002) Regional analysis of whole cell currents from hair cells of the turtle posterior crista. J Neurophysiol 88:3259-78
Goldberg, J M; Brichta, A M (1998) Evolutionary trends in the organization of the vertebrate crista ampullaris. Otolaryngol Head Neck Surg 119:165-71
Brichta, A M; Goldberg, J M (1998) The papilla neglecta of turtles: a detector of head rotations with unique sensory coding properties. J Neurosci 18:4314-24
Lysakowski, A; Goldberg, J M (1997) A regional ultrastructural analysis of the cellular and synaptic architecture in the chinchilla cristae ampullares. J Comp Neurol 389:419-43

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