Cortical circuits and information flow during memory-guided perceptual decisions

记忆引导的感知决策过程中的皮层回路和信息流

• 批准号: 8826872
• 负责人: MRIGANKA SUR
• 金额: $ 80.99万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826872
• 关键词: Address; Algorithms; Animals; Area; Behavior; Behavioral; Brain; Brain region; Calcium; Calcium Signaling; Cells; Cholera Toxin; Cognitive; Collaborations; Complex; Computer Analysis; Data; Data Set; Decision Making; Discrimination; Exhibits; Fluorescent Dyes; Genetic; Goals; Head; Image; Individual; Information Storage; Label; Light; Link; Measures; Mediating; Memory; Modeling; Molecular; Molecular Analysis; Morphologic artifacts; Motor; Motor Cortex; Movement; Mus; Neurons; Noise; Opsin; Optics; Parietal; Parietal Lobe; Pathway interactions; Pattern; Play; Population; Presynaptic Terminals; Primates; Process; Proteins; Rabies virus; Recruitment Activity; Research; Role; Sensory; Short-Term Memory; Statistical Methods; Stimulus; Techniques; Testing; Time; Tracer; Training; Transgenic Mice; V1 neuron; Visual; Visual Cortex; association cortex; awake; calcium indicator; cell type; computerized tools; driving behavior; information model; information processing; inhibitory neuron; multidisciplinary; neuromechanism; nonhuman primate; novel; optogenetics; presynaptic; public health relevance; relating to nervous system; response; signal processing; tool; two-photon

 DESCRIPTION (provided by applicant): Perceptual decision-making involves multiple cognitive components and diverse brain regions. To perform a perceptual decision, an individual must process an incoming sensory percept, retain this information in short- term memory, and choose an appropriate motor action. Research using delayed-response tasks in nonhuman primates has revealed that sensory and choice information is distributed across a hierarchy of cortical areas, with task-relevant information flowing from sensory to association to motor regions. However, a mechanistic understanding of how circuits in these regions transform and maintain information during such tasks is lacking, due to limited ability to identify and manipulat specific circuits in the primate brain. By developing a memory- guided task for head-fixed mice, we intend to leverage the genetic tractability of the mouse to address these questions. We have developed a perceptual decision task for mice that involves separate sensory, memory, and action epochs. Using large-scale population calcium imaging (Aim 1), we can simultaneously measure the activity of 1000+ neurons during the task, and across multiple brain regions (visual, parietal, and frontal motor cortex). This will allow us to record how neural activity in different cortical areas correlates with different epochs of the task. Our preliminary results indicate a diversity of different response types in each of the three areas studied, including delay-period activity in a large proportion of parietal and motor cortical neurons. These huge and complex data sets require us to employ new statistical methods (Aim 2) to analyze cell-type-specific and region-specific population activity patterns. In collaboration with Emery Brown, we will use state-space approaches to infer how single cells and cortical areas encode information about the task. To investigate the specific circuits and projection pathways underlying the task (Aim 3), we will use retrograde tracers such as rabies virus (in collaboration with Ian Wickersham) to label neurons that project to a particular brain region, or even to a single task-responsive neuron, and measure their functional role during the task. In collaboration with Kwanghun Chung, we will then use CLARITY for multiple-protein immunostaining of the entire brain. These techniques in combination will allow us to link the molecular identity and connectivity profile of each neuron with its functional role in the task. Finally, we plan to test the causal role of these brain regios and circuits using novel ontogenetic tools (Aim 4). Using transgenic mice that express ChR2 in inhibitory neurons, we will transiently inactivate each brain region during specific epochs of the task. This will allow us to determine the necessity and time course of involvement of each brain region. We will lastly manipulate the activity of anatomically-defined and computationally-identified subsets of neurons within each brain region, to determine whether specific subpopulations play a causal role in behavior. By integrating a wide range of cutting-edge experimental and computational tools, and assembling a collaborative team with multidisciplinary expertise, we hope to transform understanding of the neural substrates underlying memory-guided perceptual decisions.

 描述（由申请人提供）：感知决策涉及多个认知组件和不同的大脑区域。为了执行知觉决策，个体必须处理传入的感觉感受，将此信息保留在短期记忆中，并选择适当的运动动作。在非人类灵长类动物中使用延迟反应任务的研究表明，感觉和选择信息分布在皮层区域的层次结构中，与任务相关的信息从感觉区域流向联想区域，再流向运动区域。然而，由于识别和操纵灵长类动物大脑中特定回路的能力有限，因此缺乏对这些区域中的回路如何在此类任务中转换和维持信息的机械理解。通过为头部固定的小鼠开发记忆引导任务，我们打算利用小鼠的遗传易处理性来解决这些问题。我们已经为小鼠开发了一种感知决策任务，涉及单独的感觉，记忆和动作时期。使用大规模群体钙成像（Aim 1），我们可以在任务期间同时测量1000多个神经元的活动，并跨越多个大脑区域（视觉，顶叶和额叶运动皮层）。这将使我们能够记录不同皮层区域的神经活动如何与任务的不同时期相关联。我们的初步结果表明，在每一个不同的反应类型的多样性研究的三个领域，包括延迟期活动的顶叶和运动皮层神经元的大比例。这些庞大而复杂的数据集要求我们采用新的统计方法（目标2）来分析细胞类型特异性和区域特异性的群体活动模式。在与埃默里·布朗的合作中，我们将使用状态空间方法来推断单细胞和皮层区域如何编码有关任务的信息。为了研究任务背后的特定回路和投射通路（目标3），我们将使用狂犬病病毒等逆行示踪剂（与Ian Wickersham合作）来标记投射到特定大脑区域的神经元，甚至是单个任务响应神经元，并测量它们在任务中的功能作用。然后，我们将与Kwanghun Chung合作，使用CLARITY对整个大脑进行多蛋白免疫染色。这些技术的结合将使我们能够将每个神经元的分子身份和连接特征与其在任务中的功能作用联系起来。最后，我们计划使用新的个体发育工具来测试这些大脑区域和回路的因果作用（目标4）。使用在抑制性神经元中表达ChR2的转基因小鼠，我们将在任务的特定时期短暂地覆盖每个大脑区域。这将使我们能够确定每个大脑区域参与的必要性和时间过程。最后，我们将操纵每个大脑区域内解剖学定义和计算识别的神经元子集的活动，以确定特定的亚群是否在行为中发挥因果作用。通过整合广泛的尖端实验和计算工具，并组建一个具有多学科专业知识的协作团队，我们希望改变对记忆引导的感知决策背后的神经基质的理解。