Synaptic Modification Induced by Natural Stimuli

描述(申请人提供)：活性依赖的突触可塑性被认为是学习和记忆的细胞基础。然而，在减少的准备中由简单的活动模式引起的突触修改与完整大脑的功能可塑性之间的关系仍然是一个悬而未决的问题。我们的目标是弥合我们对这两个水平之间的活动依赖神经可塑性的理解上的差距。在脉冲时序依赖的突触可塑性(STDP)中，突触改变的方向和大小取决于突触前和突触后的相对时序，大约在几十毫秒的数量级。理论研究强调，这种形式的可塑性是一种强大的学习规则，赋予神经电路更大的计算能力。然而，以前对STDP的研究大多使用简单的棘波模式来诱导突触修饰。这些实验可能不能为理解STDP如何在完整的大脑中运作提供足够的信息，因为在完整的大脑中，由感觉刺激引起的活动显示出复杂的时空模式。在拟议的项目中，我们将在大脑皮层脑片上进行一系列实验，以系统地描绘复杂活动模式诱导的突触修改的规则。该提案分为两个部分，解决了STDP的时间和空间属性。关于时间特性，我们开发了一个简单的唯象模型来预测复杂的棘波序列在突触修饰中的影响。在拟议项目的第一部分，我们将扩展先前的研究，并将解决有关突触修改中多个棘波之间的时间相互作用的几个问题。关于空间属性，我们的初步研究表明，突触的修饰可能取决于树突的位置。由于不同位置的突触在信息处理中可能发挥不同的功能，树突位置对突触修饰的影响可能具有重要的功能意义。在拟议项目的第二部分，我们将调查树突位置对STDP的影响。神经元放电的时间复杂性和突触连接的空间复杂性对理解中枢神经系统的功能可塑性构成了重要的挑战。这些研究将为理解自然刺激如何诱导突触改变以及它们如何影响活体神经元回路的功能提供重要信息。

DESCRIPTION (provided by applicant): Activity-dependent synaptic plasticity is believed to be the cellular basis for learning and memory. However, the relationship between the synaptic modification induced by simple patterns of activity in reduced preparations and functional plasticity in the intact brain remains an open question. Our goal is to bridge the gap in our understanding of activity-dependent neural plasticity between these two levels. In spike-timing-dependent synaptic plasticity (STDP), the direction and magnitude of synaptic modification depends on the relative timing of the pre- and postsynaptic spikes on the order of tens of milliseconds. Theoretical studies have highlighted this form of plasticity as a powerful learning rule that endows neural circuits with increased computational capacity. However, most of the previous studies on STDP used simple spike patterns to induce synaptic modification. These experiments may not provide sufficient information for understanding how STDP operates in the intact brain, where activity evoked by sensory stimuli exhibit complex spatiotemporal patterns. In the proposed project, we will carry out a series of experiments in cortical slices to systematically delineate the rules governing synaptic modifications induced by complex patterns of activity. The proposal is divided into two parts, addressing the temporal and the spatial properties of STDP. Regarding the temporal properties, we have developed a simple phenomenological model to predict the effects of complex spike trains in synaptic modification. In Part 1 of the proposed project, we will extend the previous study and will address several issues concerning the temporal interactions among multiple spikes in synaptic modification. Regarding the spatial properties, our preliminary studies suggest that synaptic modification may depend on dendritic location. Since synapses at different locations may serve different functions in information processing, the effect of dendritic location on synaptic modification may have important functional implications. In Part 2 of the proposed project we will investigate the effects of dendritic location on STDP. The temporal complexity of neuronal spiking and the spatial complexity of synaptic connections pose important challenges for understanding functional plasticity in the central nervous system. The proposed studies will provide important information for understanding how synaptic modifications are induced by natural stimuli and how they affect the functions of neuronal circuits in vivo.