Glutamate release at inhibitory synapses in developing auditory system

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DESCRIPTION (provided by applicant): The long term goal of this research is to provide understanding of the rules and mechanisms by which auditory circuits in the developing mammalian brain become established and functionally optimized. Proposed experiments are aimed to provide more insight into the mechanisms by which an inhibitory sound localization pathway, the glycinergic pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) becomes topographically refined. Previous studies demonstrated that, during the period of topographic refinement, individual synapses in the developing MNTB-LSO pathway not only release the inhibitory neurotransmitters glycine and GABA, but also release the excitatory transmitter glutamate. The specific aims of the proposed application are (a) to investigate how glutamate co-release and postsynaptic glutamate receptors contribute to the generation of postsynaptic calcium responses in LSO dendrites, and (b) test the hypothesis that MNTB-LSO synapses are organized on a subcellular level according to their functional neurotransmitter phenotype. These aims are addressed using a combination of 2-photon calcium imaging and whole-cell patch clamp recordings applied to brainstem slices from neonatal mice. The results from proposed experiments will be important for better understanding normal and abnormal auditory circuit development and thus may provide insights into the biological basis of human communication disorders, such as language disabilities and dyslexia that are thought to arise from abnormal development. Summery in lay language: Anatomical and functional fine-tuning of immature brain circuits are important milestones for the normal development of hearing. Proposed research plans to apply state-of-the-art physiological techniques to investigate mechanism of neuronal communication in a mouse sound localization circuit. Results from these studies may provide better understanding of the biological basis that underlie auditory disorders including language disabilities and dyslexia which ultimately can lead to new strategies of alleviating or curing these disabilities.