Current theories regarding encoding and processing of auditory information have as their starting point a large body of detailed information on response properties of single auditory nerve fibers in cats, yet our understanding of the underlying organization of the primary afferent inputs to the cochlear nucleus (CN) is remarkably limited. The overall objective of the proposed studies is to provide fundamental information about the morphological organization and connections of cochlear spiral ganglion neurons in adult cats. Physiological recording and cytochemical labeling techniques combined with extensive light and electron microscopic analyses will be employed in these studies. Among our objectives are the following: 1) To map in fine detail the topography of the spinal ganglion projection to ventral cochlear nucleus subdivisions and cell types, utilizing HRP microinjections into the spinal ganglion; and in these experiments, to further define how the frequency representational dimension and intraganglionic vertical position project in detail onto the striking """"""""isofrequency laminae"""""""" of the major subdivisions of the CN. 2) To determine how spiral ganglion cells subserving different known classes of IHC afferent terminals are distributed in their projections across the vertical and longitudinal dimensions of Rosenthal's canal. 3) To define the topographic distributions of certain physiological response properties (among them, characteristic frequency, threshold, spontaneous discharge rate, latency, Q-10dB) within and between the """"""""isofrequency laminae"""""""" of ventral cochlear nucleus divisions, and to relate those findings to the morphology of CN projection patterns demonstrated in HRP experiments. 4) To determine whether CN projection patterns remain static or undergo topographic reorganization after ototoxic drug induction of profound sensorineural deafness and consequent severe degeneration and alteration of spiral ganglion neurons. These proposed experiments will define in much richer detail the organization of the cochlear projections to the CN, and thereby increase our understanding of the anatomical framework of the information processing machinery of the peripheral auditory system. Such data are important for formulating more complete models of the central processing of auditory information and should be of critical interest to many investigators. Proposed studies in pathological cochleas are of clinical significance, as they further define: 1) factor(s) that induce degeneration of the cochlear nerve; and 2) the nature of the CN projections from ganglion cells surviving severe deafness pathology. Data from these unique studies documenting the time course and extent of alteration in CN inputs after deafness onset have practical implications regarding the efficacies and optimization of cochlear implants in patients with similar pathologies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000160-11
Application #
3215931
Study Section
Hearing Research Study Section (HAR)
Project Start
1980-07-01
Project End
1993-03-31
Budget Start
1991-12-01
Budget End
1993-03-31
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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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
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
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