The anteroventral cochlear nucleus (AVCN) projects to the contralateral but not ipsilateral medial nucleus of the trapezoid body (MNTB). This circuitry is essential for the computation of interaural intensity differences used in sound localization. In gerbils, after deafferentation, the ipsilateral AVCN undergoes cell death and the intact AVCN innervates MNTB on both sides of the brain. The formation and plasticity of these pathways requires cellular communication through signaling molecules, which have not yet been unidentified. The Eph proteins, including Eph receptor tyrosine kinases and their ligands, the ephrins, are good candidate molecules for these processes, as they have demonstrated roles in axon guidance, map formation, and plasticity, and appear to be necessary for some aspects of development in the chick auditory brainstem. The overall goal of the proposed experiments is to determine the role(s) of Eph proteins in the specificity and tonotopy of mammalian auditory brainstem projections both during development and in response to postnatal deafferentation. In the first set of experiments, I will identify the patterns of Eph protein expression in the developing mouse brainstem and determine whether these patterns are altered by deafferentation via cochlear ablation. In the second set of experiments, I will determine whether Eph proteins are necessary for the formation of specificity and tonotopy in brainstem connections. In the third set of experiments, I will evaluate the extent and tonotopy of novel projections in the mouse brainstem in response to deafferentation, and determine whether Eph proteins mediate such plasticity. Taken together, these experiments are designed to further our understanding of the mechanisms underlying both the organization of brainstem connections during development, and the re-organization of connections that occurs in response to injury. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DC007538-03
Application #
7247823
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Cyr, Janet
Project Start
2005-07-01
Project End
2007-09-30
Budget Start
2007-07-01
Budget End
2007-09-30
Support Year
3
Fiscal Year
2007
Total Cost
$15,162
Indirect Cost
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hsieh, Candace Y; Hong, Cindy T; Cramer, Karina S (2007) Deletion of EphA4 enhances deafferentation-induced ipsilateral sprouting in auditory brainstem projections. J Comp Neurol 504:508-18
Hsieh, Candace Y; Cramer, Karina S (2006) Deafferentation induces novel axonal projections in the auditory brainstem after hearing onset. J Comp Neurol 497:589-99