Multi-regional neural circuit dynamics underlying short-term memory

短期记忆的多区域神经回路动力学

基本信息

批准号：
10241924
负责人：
Shaul Druckmann
金额：
$ 61.69万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10241924
关键词：
Address Algorithms Alzheimer&apos s Disease Anatomy Animals Anterior Area Atlases BRAIN initiative Behavior Behavior monitoring Behavioral Behavioral Paradigm Biophysical Process Brain Brain region Cerebellum Code Cognitive Data Data Set Decision Making Disease Etiology Event Functional disorder Funding Opportunities Future Gene Expression Goals Grant Individual Knowledge Link Maps Mediating Memory Methods Midbrain structure Modeling Movement Multiregional Analyses Mus Nature Neurons Outcome Pathway Analysis Pattern Population Dynamics Psyche structure Publishing Reading Recovery Rest Route Sensory Short-Term Memory Signal Transduction Silicon Site Standardization Structure System Techniques Technology Thalamic structure Volition Work base brain size cognitive function cognitive process control trial density driving behavior experience experimental analysis experimental study flexibility frontal lobe information model innovation loss of function multimodality neural circuit predicting response relating to nervous system response sensory discrimination spatiotemporal theories

项目摘要

Abstract The focus of this BRAIN Initiative funding opportunity is to use “innovative approaches to understand how circuit activity gives rise to a specific behavior”. Cognitive behaviors arise from collective interactions of multiple brain systems. Yet, for most cognitive processes, we do not yet know which brain areas are involved and how multi-regional interactions mediate specific cognitive processes. This gap in knowledge arises because separate parts of the brain are studied individually, yet, the brain circuits driving behavior vary from one behavior to another. The goal of this proposal is to establish a working example of how brain-wide activity dynamics collectively generate one cognitive behavior. We address this question by studying how a mouse flexibly generate a volitional movement based on short-term memory. Neurons in multiple parts of the brain, including the frontal cortex, thalamus, midbrain, and cerebellum respond robustly during this short-term memory and causally contribute to the behavior. Taking advantage of this opportunity to establish how activity distributed across multiple brain systems orchestrates one coherent behavior, in this proposal, we will use newly developed experimental frameworks to analyze the underlying neural circuitry at brain-wide scale and establish causal relationships between specific activity patterns and behavior. First, we will use brain-wide loss-of-function screen, high-density silicon probe recording, and anatomical techniques to produce multi- modal maps of core neural substrates of the short-term memory. The outcome datasets will be put into standardized brain coordinates, making it possible to link the functional data to existing connectional and gene expression atlases. Next, we will use simultaneous recordings and spatiotemporally-precise perturbations to probe multi-regional interactions underlying the observed activity patterns and relationships to behavior. Finally, we will build multi-regional models that offer interpretable description of the behaviorally-relevant dynamics and relate them to underlying circuit connectivity. The outcome will disambiguate competing models of how information distributed over multiple brain regions is coordinated during cognitive processes, how information is dynamically routed and gated. The experimental, analysis, and modeling approaches will be broadly useful for analyzing distributed circuits driving behavior, as is the focus of multiple collaborative U19 grants. All the data and code will be published in the well document Neurodata Without Border (NWB) format.

抽象的这项大脑计划资助机会的重点是使用“创新方法来了解如何电路活动引起了特定的行为”。认知行为是由集体互动引起的多个大脑系统。但是，对于大多数认知过程，我们尚不知道涉及哪些大脑区域以及多区域相互作用如何介导特定的认知过程。知识的差距出现因为大脑的单独部分是单独研究的，所以驱动行为行为的大脑电路因一种行为。该提案的目的是建立一个工作的示例，说明如何脑部活动动态集体产生一种认知行为。我们通过研究鼠标如何解决这个问题灵活地基于短期记忆产生意志运动。大脑多个部分的神经元，包括额叶皮层，丘脑，中脑和小脑在短期内做出了强烈反应记忆，有时会导致行为。利用这个机会确定如何活动分布在多个大脑系统中，协调一个连贯的行为，在此提案中，我们将使用新开发的实验框架，以分析脑部范围和在特定活动模式和行为之间建立因果关系。首先，我们将使用大脑功能丧失屏幕，高密度硅探针记录和解剖技术可产生多种短期记忆的核心神经基材的模态图。结果数据集将被放入标准化的大脑坐标，使功能数据与现有连接和基因联系起来是可能的表达地图。接下来，我们将使用简单的记录和空间临时扰动探测观察到的活动模式和与行为关系的基础的多区域相互作用。最后，我们将建立多区域模型，以提供与行为相关的可解释描述动态并将它们与基础电路连接联系起来。结果将消除竞争模型的歧义关于在认知过程中分布在多个大脑区域上的信息如何协调的信息是动态路由和封闭式的。实验，分析和建模方法将是对于分析分布式电路行驶行为非常有用，多个协作U19的重点也是如此赠款。所有数据和代码都将在没有边框（NWB）格式的井文中发布。