LINKING SYNAPTIC PROPERTIES TO NEURAL NETWORK OPERATION

描述：（申请人摘要的逐字逐句）本提案的目标 是为了理解神经元活动之间的相互作用 网络和连接单个神经元的突触的属性。 这些实验的基本原理是基于最近的发现， 海马CA 3区的同步网络活动的许多方面是 由突触能的循环侧支突触的特性决定 连接CA 3区锥体细胞例如，同步CA 3网络活动 不是通过反馈抑制，而是通过抑制反复出现的 侧支突触;此外，复发侧支突触的强度 确定启动同步网络活动的概率，但 而不是决定该活动的持续时间。我们建议开发这些 通过测试2个相关假设的初步结果。一、同步激活 的CA 3网络是由经常性的可量化的属性， CA 3细胞之间的侧支突触：可释放谷氨酸的供应， 谷氨酸释放的可能性和突触后决定因素 实力第二，在适当的条件下，网络活跃度足够 来产生这些突触特性的短期和长期变化。我们 将使用单细胞和双细胞全细胞记录来测试这些假设。 海马切片制备。 这些研究将阐明真实的神经网络的运作原理， 例如突触可塑性如何改变网络操作。此外，本发明还提供了一种方法， 了解正常的同步网络活动是如何终止的， 描绘癫痫治疗的新目标。例如， CA 3爆发终止的突触后抑制表明GABA介导的 在至少一些神经系统中，抑制不是最佳的抗惊厥靶点。 网络，以及对突触强度和 网络活动提出了一种新的癫痫治疗方法：利用发作间期 网络活动产生一个特定的，长期削弱的突触 导致癫痫发作的原因

DESCRIPTION: (Verbatim from the Applicant's Abstract) The goal of this proposal is to understand the reciprocal interactions between the activity of a neural network and the properties of the synapses that connect the individual neurons. The rationale for these experiments is based on the recent findings that in area CA3 of the hippocampus many aspects of synchronous network activity are determined by the properties of the glutamatergic recurrent collateral synapses that connect CA3 pyramidal cells. For example, synchronous CA3 network activity is terminated not by feedback inhibition but by depression of the recurrent collateral synapses; further, the strength of the recurrent collateral synapses determines the probability of initiating synchronous network activity, but does not ,determine the duration of that activity. We propose to develop these initial results by testing 2 related hypotheses. First, synchronous activation of the CA3 network is regulated by quantifiable properties of the recurrent collateral synapses between CA3 cells: the supply of releasable glutamate, the probability of glutamate release, and postsynaptic determinants of synaptic strength. Second, under appropriate conditions, network activity is sufficient to produce both short and long-tern changes of these synaptic properties. We will test these hypotheses using single and dual whole-cell recordings in the hippocampal slice preparation. These studies will elucidate principles by which real neural networks operate, such as how synaptic plasticity alters network operation. In addition, understanding how normal synchronous network activity is terminated will delineate new targets for epilepsy therapy. For example, the minor role of postsynaptic inhibition in CA3 burst termination indicates that GABA-mediated inhibition is not the optimal anticonvulsant target in at least some neural networks, and preliminary studies on the link between synaptic strength and network activity suggest a novel epilepsy therapy: exploiting interictal network activity to produce a specific, long-term weakening of the synapses that underlie the propensity for seizures.