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.

项目概要腹侧耳蜗核 (VCN) 的 T 星状细胞形成重要的上行通路，传递信息从听觉神经到众多听觉核团的光谱信息。它们支配橄榄耳蜗传出神经分布于梯形体的腹侧核、外侧上橄榄、下丘和丘脑。在初步实验中，我们发现等频内的 T 星状细胞群层通过可增强的兴奋性突触连接双向互连。在来自 T 星状细胞的双重全细胞膜片钳记录，在突触前细胞中放电通常不会引起任何反应。 EPSC 位于突触后细胞中，除非突触前放电与突触后去极化配对。这些研究结果令人兴奋有两个原因。首先，增强作用的机制是新的并且空前的。突触后去极化增加了记录 EPSC 的可能性，EPSC 是突触前的一种功能，暗示逆行信使的参与。我们的初步结果支持假设一氧化氮充当逆行信号。目标 1 是利用切片中的细胞内记录来获得更深入地了解 T 星状细胞和 T 星状细胞之间连接增强的机制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，听觉神经纤维的突触兴奋如何影响互连的可塑性，检查通过一氧化氮途径发出信号，并测量增强作用发展和减弱的速率。第二我们的发现揭示了一种新形式的网络级中央增益控制。双向、兴奋互连表明等频层中的 T 星状细胞形成一个网络，并且可以解释如何 T星状细胞可以锐化光谱峰值的编码。这些互连也可以形成突触正反馈回路会导致听觉神经纤维损失时过度兴奋，随之而来的兴奋和抑制的脱钩。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互连对其声音编码的影响。我们将实现可以模拟单个 T 星状细胞响应特征的模型并构建互连的神经网络来了解网络连接如何促进增强。我们将检验假设兴奋性互连增强了谱峰的编码，并且需要抑制稳定网络。