Spatio-Temporal Specificity of Synaptic Plasticity

突触可塑性的时空特异性

基本信息

批准号：
7228203
负责人：
Guoqiang Bi
金额：
$ 24.72万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2008-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Activity-dependent synaptic plasticity is crucial for the development and function of the nervous system. From my previous studies, we have found that in simple networks of cultured neurons, (i) correlated pre- and postsynaptic spiking activity induces different types of synaptic modification depending on precise spike timing; and (ii) synaptic strengthening induced at one synapse appears to propagate to specific neighboring sites in a network. Such temporal and spatial specificity of spike timing-dependent plasticity (STDP) reflects intriguing cellular mechanisms and bears important consequences for the development and function of neuronal circuits. Here, we propose a series of experiments aimed at establishing a set of spatio-temporal rules for STDP and its propagation, and revealing the underlying cellular signaling mechanisms. In Aim 1, we will identify quantitative rules for the temporal integration of STDP, emphasizing the involvement of short-term plasticity and the interaction between potentiation and depression processes. In Aim 2, we will use a novel local activation method to characterize STDP at single or a small number of identified synaptic boutons and to characterize the directions, ranges and speeds of the propagation of STDP to other identified boutons. In Aim 3, we will combine imaging and electrophysiological techniques to investigate Ca 2+ dynamics in the induction and propagation of STDP, and to evaluate the contributions from different Ca 2+ sources. The proposed project, by pursuing a set of quantitative rules for synaptic modification and a mechanistic understanding of these rules, promises to bridge the gap between synaptic physiology and neural network behavior, and advance our understanding of how experience shapes the development and function of neuronal circuits in the brain. Ultimately, these studies will provide insights into and may lead to cures for human diseases in the nervous system, especially those related to learning and memory.

描述（由申请人提供）：依赖于活动的突触可塑性对于神经系统的发展和功能至关重要。从我以前的研究中，我们发现，在简单的培养神经元网络中，（i）相关的突触前和突触后尖峰活动会导致不同类型的突触修饰，具体取决于精确的尖峰时间；（ii）在一次突触下诱导的突触增强似乎传播到网络中特定的相邻位点。峰值定时依赖性可塑性（STDP）的时间和空间特异性反映了有趣的细胞机制，并对神经元回路的发展和功能产生了重要的后果。在这里，我们提出了一系列实验，旨在建立一组STDP的时空规则及其传播，并揭示下面的细胞信号传导机制。在AIM 1中，我们将确定STDP时间整合的定量规则，强调短期可塑性的参与以及增强和抑郁过程之间的相互作用。在AIM 2中，我们将使用一种新型的局部激活方法来表征单个或少数已识别的突触式胸子的STDP，并表征STDP传播的方向，范围和速度到其他已识别的胸子。在AIM 3中，我们将结合成像和电生理技术，以研究STDP诱导和传播中的Ca 2+动力学，并评估来自不同Ca 2+源的贡献。拟议的项目通过追求一组定量规则进行突触修改和对这些规则的机械理解，有望弥合突触生理学和神经网络行为之间的差距，并促进我们对经验如何塑造大脑神经元电路的发展和功能的理解。最终，这些研究将提供有关神经系统中人类疾病的洞察力，并可能导致治愈神经系统，尤其是与学习和记忆有关的疾病。