PROPAGATION OF SYNAPTIC MODIFICATION IN NEURAL NETWORKS

描述(研究人员摘要)：发展和可塑性 神经系统涉及对突触的活性依赖的修饰 关系。利用培养中的海马神经元的简单网络， 申请人最近发现，长期抑郁(LTD)由以下因素引起 在一个突触位置的重复突触活动伴随着 广泛但选择性地将抑郁症传播到其他突触 在网络中。私家侦探现在提议进一步描述这一点 突触修饰的传播现象及其潜在的研究 细胞和分子机制。目标1中的实验将确定 LTD和长时程增强(LTP)可靠的条件 谷氨酸和氨基丁酸能突触诱导的大鼠海马神经元 诱导和表达这些基因的机制 修改。目标2中的实验将进一步证实早先的 突触抑制的背向和侧向传播研究 在引入LTD后，并将这些研究扩展到包括 伴随着LTP诱导的突触修饰的传播。这个 申请者将决定时间进程、程度和持久性 传播的变化，它们依赖于离现场的距离 LTP/LTP诱导，以及突触前和/或突触后机制 传播站点上的更改。在目标3中，申请者将审查 突触能否实现多个调制的时间整合 从与同一神经元相关的另一个突触传播的信号 正在进行顺序LTD/LTP和多个 信号从不同的突触传播，经历单独的LTD/LTP。 最后，在目标4中，申请者将研究各种不同的 细胞外和细胞内信号机制在病毒传播中的形式 LTD/LTP诱导后突触的改变。加在一起，这些 研究涉及以下几个基本问题： 神经网络中的活动诱导修改。多个全细胞 从该项目首创的已定义神经网络进行录音承诺 发现与我们的基本网络相关的以前未知的网络属性 对神经系统的了解。

DESCRIPTION (Investigator's abstract): The development and plasticity of the nervous system involve activity-dependent modification of synaptic connections. Using simple networks of hippocampal neurons in culture, the applicant recently found that long-term depression (LTD) induced by repetitive synaptic activity at one synaptic site is accompanied by an extensive but selective propagation of the depression to other synapses within the network. The P.I. now proposes to characterize further this phenomenon of propagation of synaptic modification and to examine underlying cellular and molecular mechanisms. The experiments in Aim 1 will determine the conditions by which LTD and long-term potentiation (LTP) can be reliably induced at glutamatergic and GABAergic synapses in hippocampal cultures and the mechanisms underlying the induction and expression of these modifications. The experiments in Aim 2 will further confirm the earlier findings on the back- and lateral propagation of synaptic depression following the induction of LTD and extend these studies to include the propagation of synaptic modification accompanying the induction of LTP. The applicant will determine the time course, extent and persistence of propagated changes, their dependence on the distance from the site of LTP/LTP induction, and pre-and/or postsynaptic mechanisms underlying the changes at the propagated site. In Aim 3, the applicant will examine whether a synapse can achieve temporal integration of multiple modulatory signals propagated from another synapse associated with the same neuron which is undergoing sequential LTD/LTP and spatial integration of multiple signals propagated from different synapses undergoing separate LTD/LTP. Finally, in Aim 4 , the applicant will study the involvement of various forms of extra-and intracellular signaling mechanisms in the propagation of synaptic modification following the induction of LTD/LTP. Together, these studies address several fundamental issues concerning the distribution of activity-induced modifications within a neural network. Multiple whole-cell recording from defined neural networks pioneered in this project promises to uncover previously unknown network properties relevant to our basic understanding of the nervous system.