Understanding normal and abnormal brain development requires knowledge of the cellular events whereby differential experience influences the ontogeny of neural structure and function. Research in this area has achieved new and immediate clinical importance with the increasing use of cochlear implants in congenitally and prelingually hearing impaired infants. This application seeks continued funding for a research program aimed at understanding the cellular events whereby the integrity and activity of the inner influences development of brainstem auditory pathways. Three separate lines of investigation are proposed: 1) We will continue to investigate the hypothesis that intracellular calcium homeostasis plays a key role in regulating the initiation of events leading to Tran neuronal cell death of brainstem neurons in the neonatal mammalian auditory pathways. Specific studies involve comparing changes in cochlear nucleus neurons following reversible inhibition of auditory nerve activity with changes produced by destruction of the inner ear, studies of calcium homeostasis in normal neurons and those deprived of excitatory input, and studies examining the role of plasma membrane ATPases in the regulation of calcium in deprived neurons. 2) The auditory system, like other sensory systems, is particularly sensitive to peripheral pathology during early development. Our second goal is to further understand the biological basis responsible for this """"""""critical period."""""""" We will use normal and mutant mice to examine the contribution of specific genes to these changes in susceptibility. We will use micro array technology to screen for new candidate genes, and then directly assay the new gene products for their role in establishing this critical period. 2) We combine single cell labeling, electro physiology, and calcium imaging methods to study the cellular mechanisms of afferent regulation of dendritic structure. These studies make use of the unique binaural innervation of n. laminar is cells to allow spatial resolution of the relationships between afferent stimulation, calcium homeostasis, and structural dynamics of dendrites.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003829-07
Application #
6912815
Study Section
Auditory System Study Section (AUD)
Program Officer
Freeman, Nancy
Project Start
1999-05-01
Project End
2009-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
7
Fiscal Year
2005
Total Cost
$409,488
Indirect Cost
Name
University of Washington
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Sakano, Hitomi; Zorio, Diego A R; Wang, Xiaoyu et al. (2017) Proteomic analyses of nucleus laminaris identified candidate targets of the fragile X mental retardation protein. J Comp Neurol 525:3341-3359
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Seidl, Armin H; Rubel, Edwin W; Barría, Andrés (2014) Differential conduction velocity regulation in ipsilateral and contralateral collaterals innervating brainstem coincidence detector neurons. J Neurosci 34:4914-9
McBride, Ethan G; Rubel, Edwin W; Wang, Yuan (2013) Afferent regulation of chicken auditory brainstem neurons: rapid changes in phosphorylation of elongation factor 2. J Comp Neurol 521:1165-83

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