The long-term goal of this work is to understand how vestibular organs, which transduce head position and movement, function and develop. Good health depends on the normal function of these organs. Damage can lead to debilitating vertigo, dizziness and an inability to maintain steady gaze. The primary afferent neurons to vestibular organs vary in the sensitivity and time course of their responses to head movement stimuli. Some of the variation correlates with region within the sensory organ. In amniotes, a further source of variation is likely to be differences between two classes of sensory hair cell, type I and II. This application proposes to take three approaches to stimulus processing by mammalian vestibular organs, using the rodent utricle as a model.
The first aim i s to test whether there are regional and cell-type-specific differences in the properties of the hair cell's mechanosensitive transducer conductance, which converts head movement stimuli into the receptor potential. Second, the hair cells' voltage-gated potassium conductances, which shape the receptor potential, will be characterized at the molecular level by applying probes directed at candidate proteins and messenger RNA. These conductances differ substantially between type I and II hair cells.
The third aim i s to characterize the normal development of hair cells from the period of peak terminal mitoses (prenatal) to birth of the animal. At birth, mouse utricular hair cells express some voltage-gated conductances and ultrastructural analysis shows that although the utricle is immature in many ways, some cells can be recognized as type I or II. The prenatal time course of acquisition of voltage-gated conductances will be determined with whole-cell recording. The expression of voltage-gated potassium channel proteins will be followed in time with molecular probes. Prenatal morphological differentiation of the utricle will be characterized. These experiments should provide insight into early differentiation of hair cells and supporting cells, as well as determine the utility of potassium channel proteins as markers of hair cell differentiation.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Hearing Research Study Section (HAR)
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Platt, Christopher
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Baylor College of Medicine
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Eatock, Ruth Anne (2018) Specializations for Fast Signaling in the Amniote Vestibular Inner Ear. Integr Comp Biol 58:341-350
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
McLean, Will J; McLean, Dalton T; Eatock, Ruth Anne et al. (2016) Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs. Development 143:4381-4393
Schuth, Olga; McLean, Will J; Eatock, Ruth Anne et al. (2014) Distribution of Na,K-ATPase ? subunits in rat vestibular sensory epithelia. J Assoc Res Otolaryngol 15:739-54
Spoon, Corrie; Grant, Wally (2013) Biomechanical measurement of kinocilium. Methods Enzymol 525:21-43
Songer, Jocelyn E; Eatock, Ruth Anne (2013) Tuning and timing in mammalian type I hair cells and calyceal synapses. J Neurosci 33:3706-24
Spoon, Corrie; Grant, Wally (2011) Biomechanics of hair cell kinocilia: experimental measurement of kinocilium shaft stiffness and base rotational stiffness with Euler-Bernoulli and Timoshenko beam analysis. J Exp Biol 214:862-70
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
Eatock, Ruth Anne; Songer, Jocelyn E (2011) Vestibular hair cells and afferents: two channels for head motion signals. Annu Rev Neurosci 34:501-34
Kalluri, Radha; Xue, Jingbing; Eatock, Ruth Anne (2010) Ion channels set spike timing regularity of mammalian vestibular afferent neurons. J Neurophysiol 104:2034-51

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