HETEROSYNAPTIC INTERACTIONS IN NEURAL NETWORKS

描述：（申请人摘要） 突触前和突触后过程是长时程增强的基础， 抑郁症（LTP和LTD）一直是二十多年来 广泛的研究和讨论。我们最近证明了LTD的诱导 在海马神经元的一个孤立的"三联体回路"内的一对神经元之间， 培养的神经元导致突触强度的长期变化， 三重回路的未激活突触。有限责任公司向邻近地区的传播 突触后的LTD的诱导，在突触的兴奋性， 比在GABA能突触诱导后更广泛。两个关键 这些发现引起了一些问题：（1）细胞机制是什么 潜在的可塑性扩散到非激活的突触，和（2）是 "传播可塑性"是一种不同的和额外的形式的活动依赖性 对广泛研究的“诱导塑性”的修改？这个目标 应用程序是描述和开发这个更大的图片突触 可塑性，以了解活动的分布影响， 体外简化神经元网络中突触的功效。 从2到4个突触同时记录膜片钳 培养中相互连接的神经元将允许检查功效的变化， 不同神经元之间的突触连接， LTD和LTP。具体目标1是扩展我们先前关于 LTD，以检验LTP诱导的分布效应， 在培养的海马神经元的简单回路中的未激活的突触。 具体目标2将确定潜在的传播的细胞机制， 突触可塑性具体目标3将检查单个神经元是否 整合了来自局部内活动的诱导和传播可塑性， 电路.了解管理这些活动的基本原则， 局部神经元中突触的分布式活动依赖性修饰 电路对于理解学习机制至关重要， 记忆，心理健康的各个方面，以及神经系统疾病的发病机制 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.