Transmitters and receptors are the basis for communication between neurons and as such provide the fundamental basis for signal processing in the central nervous system. Changes in transmitters and receptors also underlie many disorders and diseases of the nervous system. The proposed studies are part of a long-term research program to identify the major neurotransmitters and receptors of the auditory pathways and localize them to specific cells, terminals, synapses and pathways. Receptors have a diversity based on many sub-types and sub-units which confer different functional properties. The first two new specific aims are based on the hypothesis that receptor components will vary in different cells and synapses based on functional requirements.
SPECIFIC AIM ONE : Identify and compare amino acid receptor sub-types expressed in specific cell types of cochlear nucleus (CN) and superior olivary complex (SOC).
SPECIFIC AIM TWO : Characterize-and compare receptors apposing different terminals synapsing on VCN bushy cells and LSO principal cells. Terminals are differentiated by a) transmitter or transmitter combinations, b) origin, c) morphological criteria.
Specific aim one will utilize in situ hybridization and examine expression of receptors, specific aim two will use immunocytochemistry to look at receptor component placement and how it relates to characteristics of terminals. While these specific aims examine how transmitters and receptors shape and modify the micro-processing of auditory input, the final specific aim asks if the opposite can also be true; if auditory input can shape and modify transmitters and receptors. It tests the hypothesis that the molecular substrate of function can react and adapt to decreased auditory activity by changes in amino acid receptors and receptors. This will be tested using in situ hybridization (receptors), immunocytochemistry (receptors and transmitters) and receptor autoradiography (ligand binding).
SPECIFIC AIM THREE : Determine if there are changes in transmitters and receptors as a consequence of changes in activity caused by deafness. Proposed studies will be valuable not only in defining the substrate underlying normal information processing in the auditory pathways, but also in understanding adaptive changes under normal and pathological conditions.
