Developmental profile of glutamate receptors in nucleus laminaris

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DESCRIPTION (provided by applicant): Understanding auditory development requires knowledge of events that influences the ontogeny of neural structure and function. This research will examine the developmental role of glutamate and its receptors in a circuit used for binaural hearing. Nucleus laminaris (NL), a third-order auditory structure in birds, provides an ideal model system to address this issue. NL receives excitatory information from nucleus magnocellularis and functionally, these glutamatergic inputs provide initial cues for sound localization. It is unclear how ionotropic glutamate receptors (iGluRs) develop in NL and more importantly, the functional role they play in synaptogenesis, synaptic refinement, and dendritic arborization. This research will characterize the developmental profile of the AMPA- and NMDA-type glutamate receptors (AMPA-R and NMDA-R, respectively) and determine how developmental changes in their biophysical response properties influence the structure and function of NL neurons. My proposed research will address a general question of synaptic development. What are the properties and developmental significances of glutamate transmission and receptor function at NL synapses? My hypotheses are: (1) excitatory postsynaptic currents (EPSCs) in NL are mediated by both AMPA- and NMDA-Rs, (2) biophysical properties of AMPA- and NMDA-Rs are regulated developmentally and tonotopically and (3) activity mediated by NMDA-Rs is essential for NL structure and function. The specific aims to test these hypotheses are: (1) characterize synaptic iGluR function developmentally and tonotopically in NL and (2) block NMDA-R activity and characterize structural and functional changes in NL. The general methods I will use to test these aims are whole-cell voltage clamp recordings from acute brainstem slices, pharmacological manipulations of iGluRs, and NMDA-R inactivation from culture brainstem slices. Lay description: The proposed research studies how excitatory events during development establish connections between auditory neurons responsible for binaural hearing. Understanding how these events influence the development of auditory properties may contribute to the improvement of appropriate therapies for individuals deprived of auditory information early in life.