Investigation into the synaptic origins of hippocampal replay

项目摘要 神经科学的一个基本目标是了解大脑的突触结构是如何产生 神经动力学这一研究领域的一个核心挑战是，神经元的电活动是在大脑中记录的。 完整的受试者，同时离体进行解剖学分析。因此，通常不可能匹配 体内记录的神经元与组织切片中研究的神经元的同一性。自20世纪60年代以来， 据推测，突触的存在应该通过突触的可靠尖峰活动来表现出来。 突触前锋电位后的突触后细胞。最近的刺激研究证实， 兴奋性和抑制性海马神经元之间的强突触可以从以下推断： 分析尖峰时序关系，从而允许同时访问部分电路连接和神经 清醒的行为主体的动力学然而，单靠扣球能揭示和不能揭示的东西的局限性 关于突触还没有得到很好的理解，因为有很多原因可以解释为什么突触前细胞中的尖峰可以 无法在突触后靶点引发一个这项工作是至关重要的，因为神经计算被认为取决于 突触强度的模式 这种计算补充增加了父母R00补助金，它寻求理解如何 海马神经元在学习后改变其顺序放电模式，这种现象被称为重放。 通过亲本R00的Aim 1，我们发现了潜在的证据，即在CA1的可塑性兴奋到抑制 突触可能是重放理论基础。然而，观察到的尖峰时间的变化可能源于 其他非突触机制。在这方面，我们要求提供资金，对地面实况进行统计分析 生物物理模拟，以确定通过分析尖峰时间可以做出什么样的因果推断 关系。许多实验室现在拥有记录行为动物的尖峰神经元的数据库。的工具 在本补充中提出的目的是通过提供一个 突触相互作用如何驱动观察到的神经尖峰模式的机制描述。

Project Summary A fundamental goal of neuroscience is to understand how the synaptic architecture of the brain gives rise to neural dynamics. A central challenge in this line of inquiry is that the electrical activity of neurons is recorded in the intact subject, while anatomical analysis is conducted ex vivo. Therefore, it is often impossible to match the identities of neurons recorded in vivo with those under study in histological sections. Since the 1960s, it has been speculated that the existence of a synapse should manifest itself through the reliable spiking activity of the postsynaptic cell after the presynaptic spike. Recent stimulation studies have confirmed that the existence of strong glutamatergic synapses between excitatory and inhibitory hippocampal neurons can be inferred from analysis of spike timing relationships, thus allowing simultaneous access to partial circuit connectivity and neural dynamics in the awake, behaving subject. However, the limits of what spiking alone can, and cannot, reveal about the synapse are not well understood, as there are many reasons why a spike in a presynaptic cell could fail to elicit one in the postsynaptic target. This work is critical since neural computation is thought to depend on the pattern of synaptic strength. This computational supplement adds to the parent R00 grant, which seeks an understanding for how hippocampal neurons change their sequential firing patterns after learning, a phenomenon known as replay. Through Aim 1 of the parent R00, we found potential evidence that plasticity at the CA1 excitatory to inhibitory synapse could be a theoretical basis for replay. However, the observed changes in spike timing could arise from other, non-synaptic mechanisms. Here, we are requesting funds for statistical analyses of ground-truth biophysical simulations to determine what causal inferences can be made through an analysis of spike-timing relationships. Many labs now possess databases of spiking neurons recorded in behaving animals. The tools proposed in this supplement aim to add another layer of understanding to these datasets by providing a mechanistic description of how synaptic interactions could drive observed patterns of neural spiking.