Plastic Synaptic Interconnections between Principal cells of the Ventral Cochlear Nucleus

项目摘要 耳蜗腹侧核（VCN）的星状细胞形成了一个重要的上行通路， 从听觉神经到许多听觉核团的光谱信息。它们支配橄榄耳蜗 斜方体腹侧核、外侧上级橄榄核、下丘和 丘脑在初步的实验中，我们已经发现，在一个缺血的T星状细胞群， 层通过可增强兴奋性突触连接双向互连。在 来自T星状细胞的双全细胞膜片钳记录，突触前细胞的放电通常诱发no 除非突触前放电与突触后去极化配对，否则EPSC在突触后细胞中。这些 这些发现令人兴奋，原因有二。首先，这种增强的机制是新的， 史无前例突触后去极化增加了记录EPSC的概率， 功能，暗示逆行信使的参与。我们的初步结果支持这一假设 一氧化氮是逆行信号目的1是使用细胞内记录切片， 更深入地了解T星状细胞之间连接增强的机制， 了解它们的来源和动力。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 通过一氧化氮途径的信号传导，并测量增强发展和消退的速率。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，兴奋性 这种相互联系表明，在一个issuellaminT星状细胞形成网络，并可以解释如何 T星状细胞可以锐化频谱峰的编码。这些相互连接也可以形成突触 正反馈回路导致听觉神经纤维丧失时的过度兴奋， 兴奋和抑制的解偶联。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它们编码声音的影响。我们将 实现模型，可以模拟单个T星状细胞的反应特征，并建立一个相互连接的 神经网络，以了解网络连接如何有助于增强。我们将检验这个假设 兴奋性相互联系增强了光谱峰的编码， 稳定网络。

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.