As part of a long range program to characterize the complete complement of synaptic inputs to identified auditory neurons, the current proposal focuses on the role of the excitatory amino acid neurotransmitter glutamate, a major transmitter between auditory neurons. We seek to identify differences in the composition of the glutamate receptors in different populations of auditory neurons in the normal adult gerbil brainstem by building upon the morphological, immunocytochemical and autoradiographic studies of cell types, synaptic terminal types and chemical markers of previous grant periods. Using newly available antibodies to glutamate receptor subunits and well established immunocytochemical methods at the light and electron microscopic level, we propose to map the distribution of glutamate receptor subunits in the cochlear nucleus, superior olivary complex, lateral lemniscus and inferior colliculus. The information generated in these studies will help define the possible combinations of subunits available in specific locations within identified neuronal cell types. Since a number of glutamate receptors have differing abilities to flux calcium, and thus to provide the substrate for plasticity in the strength of synaptic connections, we will also test the hypothesis that there is a relationship between the different glutamate receptors (especially those which flux calcium) and the localization of calcium binding proteins. Finally, we will examine changes in receptor subunit localization at postsynaptic membrane specialization in situations where the physiology and/or anatomy of the pre- and post-synaptic cells is changing: in development, during the period of reorganization and shortening of the postsynaptic membrane specialization; in aging, when one mechanism of hearing loss may be changes in the efficacy of signaling between auditory neurons which may be caused by alterations in receptors; and in animals with experimentally induced temporary or permanent hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
2R01DC000132-19
Application #
2124765
Study Section
Hearing Research Study Section (HAR)
Project Start
1987-08-01
Project End
2000-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
19
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Yale University
Department
Surgery
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520