HETEROSYNAPTIC INTERACTIONS IN NEURAL NETWORKS

描述：(申请人摘要) 长时程增强和突触后的突触前和突触后过程 抑郁症(LTP和LTD)一直是20多年来人们关注的焦点 广泛的研究和辩论。我们最近演示了LTD的诱导 在孤立的海马三联回路内的一对神经元之间 培养中的神经元导致突触强度的长期变化 三联体回路的非激活突触。有限责任公司向邻近地区的蔓延 LTD诱导的谷氨酸能突触更多 比GABA能突触诱导更广泛。两个关键问题 从这些发现引出的问题是：(1)细胞机制是什么 可塑性向非激活突触扩散的基础，以及(2)是 “传播性可塑性”--一种不同的、附加的活动依赖形式 对被广泛研究的“诱导塑性”的修正？这样做的目的是 应用程序是描述和发展突触的这个更大的图景 可塑性，以了解活动对 突触在体外简化的神经元网络中的功效。 两个至四个突触的同时膜片钳记录 培养中相互连接的神经元将允许检查疗效的变化 诱导后不同神经元之间的突触连接 有限公司和LTP。具体目标1是扩展我们之前关于流行性感冒传播的发现 LTP诱导的分布效应。 培养的海马神经元简单回路中的非激活突触。 特定目标2将决定病毒传播的细胞机制 突触可塑性。特定目标3将检查单个神经元是否 整合了来自本地活动的诱导和传播的可塑性 巡回赛。对基本原则的理解 局部神经突触的分布式活动依赖性修饰 电路对于理解学习机制是至关重要的， 记忆，精神健康的各个方面，以及神经病学的发病机制 以及老年性疾病，如癫痫和阿尔茨海默病。

DESCRIPTION: (Applicant's Abstract) The pre- and postsynaptic processes underlying long-term potentiation and depression (LTP and LTD) have been the focus of more than two decades of extensive research and debate. We recently demonstrated that induction of LTD between a pair of neurons within an isolated "triplet circuit" of hippocampal neurons in culture results in long-lasting changes in synaptic strength at non-activated synapses of the triplet circuit. The spread of LTD to neighboring synapses following induction of LTD at glutamatergic synapses was more extensive than following induction at GABAergic synapses. Two critical questions arise from these findings: (1) what is the cellular mechanism underlying the spread of plasticity to non-activated synapses, and (2) is "propagated plasticity" a different and additional form of activity-dependent modification to the extensively studied "induced plasticity"? The goal of this application is to describe and develop this larger picture of synaptic plasticity, to gain an understanding of the distributed effects of activity on the efficacy of synapses in a simplified network of neurons in vitro. Simultaneous patch-clamp recordings from two to four synaptically interconnected neurons in culture will allow examination of changes in efficacy of synaptic connections between the different neurons following induction of LTD and LTP. Specific Aim 1 is to extend our previous findings on the spread of LTD, to examine the distributed effects of the induction of LTP on non-activated synapses in the simple circuits of cultured hippocampal neurons. Specific Aim 2 will determine the cellular mechanism underlying the spread of synaptic plasticity. Specific Aim 3 will examine whether an individual neuron integrates induced and propagated plasticity from activity within the local circuit. An understanding of the fundamental principles governing the distributed activity-dependent modifications of synapses in local neural circuits will be vital to the understanding of the mechanisms of learning, memory, various aspects of mental health, and the pathogenesis of neurological and aging disorders such as epilepsy and Alzheimer's disease.