A multi-electrode study of cortical attractor networks in spatial working memory

空间工作记忆中皮质吸引子网络的多电极研究

• 批准号: 8663956
• 负责人: Charalampos Papadimitriou
• 金额: $ 2.95万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8663956
• 关键词: Alzheimer' s Disease; Animals; Architecture; Behavioral Assay; Brain; Cells; Cognition; Computer Simulation; Data; Disease; Drops; Electrodes; Functional disorder; Impairment; Individual; Location; Macaca; Measures; Memory; Mental disorders; Modeling; Neurons; Noise; Physiological; Play; Population; Prefrontal Cortex; Reading; Recruitment Activity; Relative (related person); Role; Schizophrenia; Shapes; Short-Term Memory; Structure; Testing; Time; Training; Width; behavior measurement; cognitive function; computer studies; neural circuit; neuromechanism; receptive field; relating to nervous system

DESCRIPTION (provided by applicant): We will probe the circuitry of spatial working memory using multi single-unit recording in the dorsolateral prefrontal cortex (DLPFC) to study how neuronal activity changes over long delays, and use this information to better understand the circuitry underlying working memory and spatial computations. This project will make use of multi single-unit recording to test several hypotheses regarding the spatial working memory neural architecture. Working memory plays a crucial role in many cognitive functions and as a result has become an important topic of psycophysical, physiological, and computational study. Impairments in working memory are major factors of many disorders such as Alzheimer's Disease and schizophrenia. Understanding the neural mechanisms and circuitry involved in working memory is vital for understanding cognitive functions that depend on working memory as well as for understanding the pathophysiology of related disorders. Spatial working memory decays over time. The neuronal correlates of this decay, measured at the single neuron level, will help elucidate how spatial information is encoded and how spatial working memory functions at the singe neuron and small circuit level. Single cells in DLPFC have circumscribed mnemonic fields, analogous to receptive fields (Goldman-Rakic 1987; Funahashi, Bruce, and Goldman-Rakick, 1989). We will study whether and how these fields change as memory decays. We consider this in the computational context of an attractor network, the premier model for spatial working memory (Compte et al. 2000). Aim 1: Test how the mnemonic fields of individual neurons in DLPFC change as memory decays, and relate these changes at the single cell level to a behavioral assay of memory decay over time. We will obtain tuning curves, in time and space, for the mnemonic fields of individual cells. By recording from multiple cells simultaneously, we will have both absolute and relative information about how these curves change over time, and how these changes relate to trial-by-trial changes in spatial working memory content. From these data, we will determine whether the activity bump formed by the population drifts, drops in amplitude, broadens or thins out over a long delay period. We will also determine which of these changes are correlated with changes in memory decay as reflected in behavioral measures. Aim 2: Test the generality of the spatial working memory mechanisms revealed in Aim 1 by comparing the neuronal correlates of storing a single spatial location with multiple locations. We will construct tuning curves when a macaque is holding two spatial locations in working memory and examine how these tuning curves compare to tuning curves generated when each of the same two locations is maintained individually. We will consider and test hypotheses of a single spatial working memory network vs. multiple independent networks, as well as hypotheses of alternative strategies such as maintaining relative relationships between a set of locations (e.g. remembering a line instead of two locations).

描述（由申请人提供）： 我们将使用背外侧前额叶皮层（DLPFC）中的多个单单位记录来探索空间工作记忆的回路，以研究神经元活动如何在长时间延迟中变化，并使用这些信息来更好地理解工作记忆和空间计算的回路。本研究将利用多个单单位的记录来检验关于空间工作记忆神经结构的几个假设。工作记忆在许多认知功能中起着至关重要的作用，因此已成为心理物理学、生理学和计算研究的重要课题。工作记忆的损伤是许多疾病如阿尔茨海默病和精神分裂症的主要因素。了解工作记忆中涉及的神经机制和电路对于理解依赖于工作记忆的认知功能以及理解相关疾病的病理生理学至关重要。空间工作记忆会随着时间的推移而衰退。在单个神经元水平上测量这种衰减的神经元相关性，将有助于阐明空间信息是如何编码的，以及空间工作记忆在单个神经元和小回路水平上是如何发挥作用的。DLPFC中的单个细胞具有与感受野类似的限定记忆野（Goldman-Rakic 1987; Funahashi，布鲁斯和Goldman-Rakick，1989）。我们将研究这些场是否以及如何随着记忆衰退而变化。我们在吸引子网络的计算环境中考虑这一点，吸引子网络是空间工作记忆的首要模型（Compte et al. 2000）。目标1：测试DLPFC中单个神经元的记忆场如何随着记忆衰退而变化，并将单细胞水平上的这些变化与记忆衰退随时间推移的行为测定相关联。我们将获得单个细胞记忆场在时间和空间上的调谐曲线。通过同时记录多个细胞的数据，我们将获得这些曲线如何随时间变化的绝对和相对信息，以及这些变化如何与空间工作记忆内容的逐个试验变化相关。从这些数据中，我们将确定由人口形成的活动隆起是否在长时间的延迟期间漂移、幅度下降、变宽或变薄。我们还将确定这些变化中哪些与行为测量中反映的记忆衰退变化相关。目标二：通过比较存储单个空间位置和多个位置的神经元相关性，测试目标1中揭示的空间工作记忆机制的一般性。我们将构建调谐曲线时，猕猴是持有两个空间位置在工作记忆中，并检查这些调谐曲线相比，调谐曲线时产生的每一个相同的两个位置分别保持。我们将考虑和测试单个空间工作记忆网络与多个独立网络的假设，以及替代策略的假设，例如保持一组位置之间的相对关系（例如记住一条线而不是两个位置）。