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Plastic Synaptic Interconnections between Principal cells of the Ventral Cochlear Nucleus

腹侧耳蜗核主细胞之间的塑料突触互连

基本信息

批准号：
10415856
负责人：
PHILIP H SMITH
金额：
$ 44.8万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-03-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10415856
关键词：
Acoustic Nerve Acoustic Stimulation Action Potentials Affect Axon Brain Stem Cell Nucleus Cells Cellular Membrane Chemosensitization Cochlear nucleus Collaborations Complex Computer Models Dendrites Exhibits Feedback Fire - disasters Frequencies Hearing Hodgkin-Huxley model Human Inferior Injections Interneurons Lead Mammals Measurement Measures Mediating Modeling Mus N-Methyl-D-Aspartate Receptors Nerve Fibers Neurons Neurotransmitters Nitric Oxide Nitric Oxide Donors Nitric Oxide Pathway Nitric Oxide Synthase Type I Oxides Pathway interactions Pharmacology Physiological Play Positioning Attribute Probability Property Role Sensitivity Training Groups Signal Pathway Signal Transduction Slice Soluble Guanylate Cyclase Source Speech Speech Sound Synapses Synaptic plasticity Testing Thalamic structure Work auditory nuclei auditory pathway base dorsal cochlear nucleus experimental study extracellular hearing impairment lateral superior olive models and simulation neural model neural network novel patch clamp postsynaptic predicting response presynaptic response simulation sound stellate cell trapezoid body voltage

项目摘要

Project Summary T Stellate cells of the ventral cochlear nucleus (VCN) form an important ascending pathway that transmits spectral information from the auditory nerve to numerous auditory nuclei. They innervate the olivocochlear efferents in the ventral nucleus of the trapezoid body, the lateral superior olive, the inferior colliculi and the thalamus. In preliminary experiments we have discovered that groups of T stellate cells within an isofrequency lamina are bidirectionally interconnected through excitatory synaptic connections that can be potentiated. In dual, whole-cell patch-clamp recordings from T stellate cells, firing in a presynaptic cell generally evoked no EPSCs in the postsynaptic cell unless presynaptic firing was paired with postsynaptic depolarization. These findings are exciting for two reasons. First is that the mechanism underlying that potentiation is new and unprecedented. Postsynaptic depolarization increased the probability of recorded EPSCs, a presynaptic function, implicating the involvement of a retrograde messenger. Our preliminary results support the hypothesis that nitric oxide serves as that retrograde signal. Aim 1 is to use intracellular recordings in slices to gain a deeper understanding of the mechanisms that underlie potentiation of connections between T stellate cells and to understand their source and dynamics. We will identify what neurons participate in polysynaptic connections, how synaptic excitation by auditory nerve fibers affects the plasticity of interconnections, examine signaling through the nitric oxide pathway, and measure rates at which potentiation develop and fade. Second is that our discovery reveals a new form of central gain control at the network level. Bidirectional, excitatory interconnections indicate that T stellate cells in an isofrequency lamina form a network and could explain how T stellate cells can sharpen the encoding of spectral peaks. These interconnections could also form synaptic positive feedback loops that lead to hyperexcitability in the face of loss of auditory nerve fibers and the consequent uncoupling of excitation and inhibition. Aim 2 is to use computational neural models to understand the implications of excitatory interconnections between T stellate cells on their encoding of sound. We will implement models that can simulate the response features of single T stellate cells and build an interconnected neural network to understand how network connectivity contributes to potentiation. We will test the hypothesis that excitatory interconnections enhance the encoding of spectral peaks and that inhibition is required to stabilize the network.

项目总结