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如何产生 神经动力学。这一系列研究的一个中心挑战是，神经元的电活动被记录在 完整的受试者，而解剖分析是在体外进行的。因此，通常不可能匹配 活体记录的神经元与组织切片中正在研究的神经元的一致性。自20世纪60年代以来，它一直 已经推测，突触的存在应该通过可靠的突触活动来体现 突触前峰后的突触后细胞。最近的刺激研究证实， 兴奋性和抑制性海马神经元之间强烈的谷氨酸能突触可以从 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、行为的主体的动力学。然而，尖峰效应本身的局限性可以揭示，也不能揭示。 关于突触的了解还不是很清楚，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 未能在突触后靶区引出一个。这项工作至关重要，因为神经计算被认为依赖于 突触力量的模式。 这一计算补充添加到父R00奖励中，该奖励寻求了解如何 海马神经元在学习后改变了它们的顺序放电模式，这种现象被称为重播。 通过亲本R00的目标1，我们发现了CA1可塑性兴奋到抑制的潜在证据 突触可能是重播的理论基础。然而，观察到的尖峰时序的变化可能源于 其他非突触机制。在这里，我们正在申请资金，用于对实地情况进行统计分析。 生物物理模拟，以确定可以通过分析尖峰时间作出什么因果推断 两性关系。许多实验室现在拥有记录动物行为的尖峰神经元的数据库。这些工具 本附录中提出的建议旨在通过提供一个 突触相互作用如何驱动观察到的神经尖峰模式的机械性描述。

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.