Studying Memory Retrieval at the Dynamic Neural Network Level

 描述(由申请人提供)：神经科学中的一个基本问题是，记忆是如何通过神经群体中的集体尖峰模式来表示的。一个相关的问题是，在学习过程中用来代表记忆的相同集体模式在后来的回忆中是否被重新激活，或者种群代码的性质是否完全不同。虽然先前的理论工作和最近在动物模型中的工作已经为记忆可能是如何表征的提供了有价值的初步见解，但在整个网络水平上实际提取记忆的神经过程，一阶、二阶和更高阶网络结构的哪些确切方面是关于所提取的记忆的信息，以及这些信息模式在个体试验中以何种快速的亚秒动态演变，仍然是根本未知的。这种有限的理解尤其适用于异质联想记忆过程，例如线索回忆，在这种记忆过程中，被回忆的物品既不存在，也与用于提示其提取的呈现物品完全不同。在这里，我们的目标是第一次系统地定义构成这些基本形式的自联想(再认)和异联想(回忆)记忆的组合的网络级过程。为此，我们将利用两位主要研究人员的共同专业知识，从猕猴的额叶和颞叶皮质种群进行同时的多电极记录；设计和测试新的分析方法，既可以可靠地从随机尖峰数据中推断集体的一阶、二阶和更高阶功能网络结构；跟踪它们在个别试验中的快速亚秒动态；确定哪些结构对被回忆的记忆具有信息性；确定在学习过程中观察到的尖峰网络结构何时以及在多大程度上被激活；而且，也许最重要的是，确定在尖峰网络水平上的模式重新激活是否与行为水平上的回忆准确性存在因果关系。目前的提议将使我们能够第一次直接检验一些中心假设 使用一套新的技术和方法创新的记忆处理，将对与记忆相关的发育、行为和神经退行性疾病的研究具有广泛的实际意义。

 DESCRIPTION (provided by applicant): A fundamental question in neuroscience is how memories are represented by the collective pattern of spiking within neural populations. A related question is whether the same collective pattern used to represent memories during learning are "reactivated" during later recall, or if the nature of the population code is vitally different. While prior theoretical work and more recent work in animal models have provided valuable initial insights into how memories are likely represented, the neural process by which memories are actually retrieved at the network-wide level, what exact aspects of the first-, second- and higher-order network structure are informative of the retrieved memories, and by what rapid sub-second dynamic do such informative patterns evolve within individual trials remain fundamentally unknown. This limited understanding is particularly true of hetero-associative memory processes such as cued recollection in which the items being recalled are both absent and completely unique from the presented items used to cue their retrieval. Here, we aim to systematically define, for the first time, the combined network-level processes that underlie these basic forms of auto-associative (recognition) and hetero-associative (recollection) memory. Towards these ends, we will use the shared expertise of the two principal investigators to perform simultaneous multi-electrode recordings from frontal and temporal cortical populations in Rhesus macaques; devise and test novel analysis methodologies that can both reliably infer the collective first-, second- and higher-order functional network structures from stochastic spiking data; track their rapid sub-second dynamics within individual trials; identify which structures are informative of the memories being recalled; determine when and to what extent spiking network structures observed during learning reactivate during recall within individual-day sessions; and, perhaps most importantly, determine whether pattern reactivation, at the spiking network-level, is causatively related to recall accuracy at the behavioral level. Th present proposal will allow us to directly test, for the first time, a number of central hypotheses on memory processing using a novel set of technical and methodological innovations that will have broad practical implications to the study of memory-related developmental, behavioral and neurodegenerative disorders.