PREFRONTAL CIRCUITS OF WORKING MEMORY

工作记忆的前额回路

• 批准号: 10446082
• 负责人: CHRISTOS CONSTANTINIDIS
• 金额: $ 72.42万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446082
• 关键词: Action Potentials; Address; Age-associated memory impairment; Alzheimer' s Disease; Area; Attention; Basic Science; Brain; Cells; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Complex; Coupled; Cues; Elements; Exhibits; Foundations; Future; Generations; Health; Impaired cognition; Influentials; Interneurons; Intervention; Knowledge; Macaca; Maintenance; Mediating; Memory; Mental disorders; Methods; Modeling; Monkeys; Neurodegenerative Disorders; Neurons; Parvalbumins; Play; Population; Positioning Attribute; Prefrontal Cortex; Primates; Property; Recurrence; Rodent; Role; Schizophrenia; Short-Term Memory; Somatostatin; Specificity; Stimulus; Stroke; Testing; Training; Transfection; Traumatic Brain Injury; Vasoactive Intestinal Peptide; Viral; Visuospatial; Work; awake; base; cognitive function; cognitive task; design; effective therapy; experimental study; extracellular; hippocampal pyramidal neuron; insight; neural circuit; neural correlate; neuronal circuitry; neurophysiology; nonhuman primate; normal aging; operation; optogenetics; predictive modeling; receptive field; relating to nervous system; response; success; treatment strategy

PROJECT SUMMARY/ABSTRACT Working memory, the ability to maintain and manipulate in formation in memory over a period of seconds, is a critical component of higher cognitive functions. Neurons in the prefrontal cortex and other brain areas continue to discharge during the maintenance of working memory however, little direct evidence exists on how neurons of different types organize into functional circuits to subserve these functions. A theoretical proposal, known as the Division-of-Labor model, has proposed that different types of interneurons in the prefrontal cortex play distinct roles with respect to attention. We propose to test the model in an awake, behaving non-human primate model. We will focus on one interneuron type, that expressing somatostatin, which we will identify through viral transfection and optogenetic methods. We will characterize the response properties of SST neurons in awake behaving monkeys performing visual-spatial attention tasks, determine the relative contributions of SST neurons in the local circuit that is activated during the task, and manipulate their activity through optogenetic means. This project will allow us the unprecedented ability to characterize and manipulate a neural circuit that controls a higher cognitive function (working memory) as model of understanding the circuits that underlie higher cognition.

项目概要/摘要 工作记忆是在几秒钟内维持和操纵记忆中的信息的能力，是一种 高级认知功能的关键组成部分。前额皮质和其他大脑区域的神经元 然而，在工作记忆维持期间继续放电，但很少有直接证据表明如何 不同类型的神经元组织成功能回路以促进这些功能。一个理论建议， 被称为分工模型，提出前额皮质中不同类型的中间神经元 在注意力方面发挥着不同的作用。我们建议在清醒的、有行为能力的非人类身上测试该模型 灵长类动物模型。我们将重点关注一种表达生长抑素的中间神经元类型，我们将识别它 通过病毒转染和光遗传学方法。我们将描述 SST 的响应特性 执行视觉空间注意任务的清醒行为猴子的神经元，确定相对 SST 神经元在任务期间激活的局部回路中的贡献，并操纵它们的活动 通过光遗传学手段。这个项目将使我们获得前所未有的表征和操纵能力 控制高级认知功能（工作记忆）的神经回路，作为理解事物的模型 构成更高认知的电路。