EXCEED THE SPACE PROVIDED. This proposed research addresses specific questions regarding the development of the cochlea and the establishment of the topographic organization of spiral ganglion projections to the cochlear nuclei (CN). Cytochemical labeling techniques (NB and Dil) for neuronal tract tracing combined with electrophysiological recording and extensive quantitative light and electron microscopic analyses will be employed. Our recent studies have shown that projections from basal sectors of the spiral ganglion to each subdivision of the CN undergo significant refinement during early postnatal development. Projections to the anteroventral subdivision (AVCN) are more than 50% broader in neonates than in adults when normalized for CN size, and the descending collaterals of these same neurons projecting to the dorsal (DCN) and posteroventral (PVCN) subdivisions are 30% broader than their adult counterparts. Goals of proposed experiments include: 1) To further investigate the details of timing and sequence of topographic refinement during late gestation and early postnatal development of the projections to each subdivision of the CN. 2) To examine projections from the apical cochlea to determine if maturation of its CN projections parallels the basal-to-apical maturation of the organ of Corti. 3) To complete quantitative studies of the effects of neonatal deafening upon the specificity of CN projections examined in adulthood after a lifetime of severe auditory deprivation. 4) To determine whether CN projections develop normally or if significant reorganization occurs as a consequence of restricted lesions of the spiral ganglion created during early development. 5) To determine whether anatomical remodeling of CN projections underlies the apparent loss of frequency selectivity induced by chronic intracochlear electrical stimulation. 6) To explore the mechanisms which underlie normal development of the auditory nerve projections by examining the nature of spontaneous activity (if any) in spiral ganglion. 7) To characterize selected ultrastructural features of postnatal development of the cat organ of Corti at specific frequency locations. The proposed experiments will increase our understanding of the anatomical framework for information processing mechanisms in the developing auditory system and will address important questions regarding critical periods and plasticity. In addition, studies to be conducted in deafened animals have practical implications regarding application of cochlear implants in children. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000160-23
Application #
6832842
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Freeman, Nancy
Project Start
1980-07-01
Project End
2007-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
23
Fiscal Year
2005
Total Cost
$241,264
Indirect Cost
Name
University of California San Francisco
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Leake, Patricia A; Hradek, Gary T; Bonham, Ben H et al. (2008) Topography of auditory nerve projections to the cochlear nucleus in cats after neonatal deafness and electrical stimulation by a cochlear implant. J Assoc Res Otolaryngol 9:349-72
Stakhovskaya, Olga; Hradek, Gary T; Snyder, Russell L et al. (2008) Effects of age at onset of deafness and electrical stimulation on the developing cochlear nucleus in cats. Hear Res 243:69-77
Leake, Patricia A; Stakhovskaya, Olga; Hradek, Gary T et al. (2008) Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system. Hear Res 242:86-99
Jones, Timothy A; Leake, Patricia A; Snyder, Russell L et al. (2007) Spontaneous discharge patterns in cochlear spiral ganglion cells before the onset of hearing in cats. J Neurophysiol 98:1898-908
Leake, Patricia A; Hradek, Gary T; Chair, Leila et al. (2006) Neonatal deafness results in degraded topographic specificity of auditory nerve projections to the cochlear nucleus in cats. J Comp Neurol 497:13-31
Leake, Patricia A; Snyder, Russell L; Hradek, Gary T (2002) Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats. J Comp Neurol 448:6-27
Sato, M; Leake, P A; Hradek, G T (1999) Postnatal development of the organ of Corti in cats: a light microscopic morphometric study. Hear Res 127:1-13
Leake, P A; Kuntz, A L; Moore, C M et al. (1997) Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats. Hear Res 113:117-32