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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.

项目摘要耳蜗腹核(VCN)的T星状细胞形成一条重要的上行通路，传递从听神经到众多听觉核团的光谱信息。它们支配橄榄耳蜗区斜方体腹侧核、外侧上橄榄核、下丘和下丘的传出丘脑。在初步实验中，我们发现一组T星状细胞在一个同频椎板通过兴奋性突触连接双向连接，突触连接可以增强。在……里面双细胞全细胞膜片钳记录T星状细胞，在突触前细胞放电一般诱发NO 突触后细胞中的EPSCs，除非突触前放电与突触后去极化成对。这些这一发现令人振奋，原因有二。首先，这种增强作用的机制是新的和史无前例。突触后去极化增加了记录到的突触前EPSCs的概率功能，暗示有逆行信使参与。我们的初步结果支持这一假设一氧化氮就是逆行信号。目标1是使用切片中的细胞内记录来获得更深入地理解增强T星状细胞和T细胞之间连接的机制以了解它们的来源和动态。我们将确定哪些神经元参与多突触连接，听神经纤维的突触兴奋如何影响相互连接的可塑性通过一氧化氮途径传递信号，并测量增强发展和减弱的速度。第二我们的发现揭示了网络层面的一种新的中央获得控制形式。双向、兴奋性相互连接表明，等频板中的T星状细胞形成了一个网络，并可以解释 T星状细胞可以使谱峰的编码变得清晰。这些相互连接也可以形成突触正反馈环在听神经纤维丢失时导致过度兴奋随之而来的是兴奋和抑制的分离。目标2是使用计算神经模型来理解 T星状细胞之间的兴奋性相互联系对其声音编码的影响。我们会实现能够模拟单个T星状细胞的响应特征的模型，并构建互联的神经网络，以了解网络连接如何有助于增强。我们将检验这一假设兴奋性互连增强了谱峰的编码，并且需要抑制来稳定网络。