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.

项目摘要腹侧耳蜗核（VCN）的T星状细胞形成了一个重要的上升途径，该途径传播从听觉神经到众多听觉核的光谱信息。他们支配橄榄石梯形体的腹侧核，侧面橄榄，下丘和丘脑。在初步实验中，我们发现同频率内的T星状细胞组通过可以增强的兴奋性突触连接，在双向互连薄片。在来自T星细胞的双重，全细胞斑块钳记录，发射在突触前细胞中通常诱发NO 除非突触前发射与突触后去极化配对，否则EPSC在突触后细胞中。这些发现令人兴奋，有两个原因。首先是，增强的基础机制是新的，空前的。突触后去极化增加了记录的EPSC的可能性，EPSC是一种突触前功能，暗示逆行使者的参与。我们的初步结果支持假设一氧化氮用作逆行信号。目的1是在切片中使用细胞内记录来获得对T星细胞与连接的增强基础的机制的更深入了解了解他们的来源和动态。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激发如何影响互连的可塑性，检查通过一氧化氮途径的信号传导，并测量增强和褪色的速率。第二是我们的发现揭示了在网络级别上的一种新形式的中央增益控制形式。双向，兴奋性互连表明同频层中的t星细胞形成网络，可以解释如何解释如何 T星状细胞可以锐化光谱峰的编码。这些互连也可能形成突触面对听觉神经纤维的丧失和因此，激发和抑制作用的解偶联。目标2是使用计算神经模型来了解 T星细胞之间兴奋性互连对声音编码的含义。我们将实现可以模拟单个T星细胞的响应特征并构建互连的模型神经网络了解网络连接如何有助于增强。我们将检验假设这种兴奋性互连增强了光谱峰的编码，需要抑制才能稳定网络。