Synaptic Modification Induced by Natural Stimuli

描述（由申请人提供）：活动依赖性突触可塑性被认为是学习和记忆的细胞基础。然而，突触修饰诱导的简单模式的活动在减少准备和功能可塑性在完整的大脑之间的关系仍然是一个悬而未决的问题。我们的目标是弥合这两个水平之间的活动依赖性神经可塑性的理解的差距。在尖峰定时依赖性突触可塑性（STDP）中，突触修饰的方向和幅度取决于突触前和突触后尖峰的相对定时，其量级为数十毫秒。理论研究强调这种形式的可塑性是一种强大的学习规则，赋予神经回路更高的计算能力。然而，大多数以前的研究STDP使用简单的锋电位模式诱导突触修饰。这些实验可能无法提供足够的信息来理解STDP如何在完整的大脑中运作，其中由感官刺激引起的活动表现出复杂的时空模式。在这个计划中，我们将在皮层切片中进行一系列的实验，以系统地描绘由复杂的活动模式引起的突触修饰的规则。该提案分为两个部分，处理STDP的时间和空间属性。关于时间属性，我们已经开发了一个简单的唯象模型来预测复杂的锋电位序列在突触修饰中的作用。在第一部分中，我们将扩展先前的研究，并将解决几个问题，在突触修饰的多个尖峰之间的时间相互作用。关于空间特性，我们的初步研究表明，突触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具有不同的功能，因此树突位置对突触修饰的影响可能具有重要的功能意义。在第二部分的建议项目，我们将研究树突状位置对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提出了重要的挑战。这些研究将为理解自然刺激如何诱导突触修饰以及它们如何影响体内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.