LINKING SYNAPTIC PROPERTIES TO NEURAL NETWORK OPERATION

描述：(逐字摘自申请者的摘要)本提案的目标 是为了理解神经活动之间的相互作用 网络和连接单个神经元的突触的特性。 这些实验的理论基础是基于最近的发现，在 海马区CA3同步网络活动的许多方面是 由谷氨酸能经常性侧支突触的性质决定 连接CA3锥体细胞。例如，同步CA3网络活动 不是通过反馈抑制而是通过抑制复发而终止的 侧支突触；此外，反复出现的侧支突触的强度 确定启动同步网络活动的概率，但 不，确定该活动的持续时间。我们建议开发这些 通过检验2个相关假设得到初步结果。第一，同步激活 CA3网络的大小由递归的可量化属性来调节 CA3细胞之间的侧支突触：可释放谷氨酸的供应 谷氨酸释放的概率和突触的突触后决定因素 力量。第二，在适当的条件下，网络活动是足够的 以产生这些突触属性的短期和长期变化。我们 将使用单个和双个全细胞记录来测试这些假设 海马区脑片制备。 这些研究将阐明真正的神经网络的运行原理， 比如突触的可塑性如何改变网络运作。此外, 了解正常的同步网络活动是如何终止的 勾勒出癫痫治疗的新靶点。例如，次要角色是 CA3突触终止中的突触后抑制表明GABA介导 至少在某些神经细胞中，抑制不是最佳的抗惊厥靶点 以及突触强度和突触强度之间联系的初步研究 网络活动提示一种新的癫痫治疗方法：利用发作间歇期 产生特定的、长期的突触减弱的网络活动 这是癫痫发作倾向的基础。

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.