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: 8935967
• 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/8935967
• 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; Health; 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 neurons; 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（由适用提供）：感知决策涉及多个认知成分和潜水大脑区域。要执行感知决定，个人必须处理传入的感觉知觉，将这些信息保留在短期内存中，并选择适当的电动机动作。使用非人类私人中的延迟反应任务的研究表明，感觉和选择信息分布在皮质区域的层次结构上，与任务相关的信息从感觉到关联到运动区域。但是，由于有限的识别和操纵特定电路的能力有限，因此缺乏对这些区域中的电路如何转换和维护信息的机械理解。通过为头固定小鼠开发记忆引导的任务，我们打算利用鼠标的遗传障碍来解决这些问题。我们已经使用大规模种群钙成像（AIM 1）为小鼠开发了一项感知决策任务，我们可以轻松地测量任务过程中1000多个神经元的活性，以及​​在多个大脑区域（视觉，顶点和额叶皮层）。这将使我们能够记录不同相关区域中的神经元活动与任务不同时期的相关性。我们的初步结果表明，所研究的三个区域中的每个区域中的每个区域中有多种不同的反应类型，包括大部分顶叶和运动皮质神经元的延迟至周期活性。这些巨大而复杂的数据集要求我们采用新的统计方法（AIM 2）来分析细胞类型特异性和特定区域的种群活动模式。与Emery Brown合作，我们将使用州空间方法来推断单个单元格和皮质区域如何编码有关该任务的信息。为了调查任务背后的特定电路和投影途径（AIM 3），我们将使用逆行示踪剂，例如狂犬病病毒（与伊恩·威克斯汉姆（Ian Wickersham）合作），将投射到特定大脑区域的神经元标记为特定的大脑区域，甚至将单个任务响应性神经元投射到任务中的功能。然后，与Kwanghun Chung合作，我们将使用Clarity进行整个大脑的多蛋白免疫染色。这些结合的技术将使我们能够将每个神经元的分子身份和连通性谱与其在任务中的功能作用联系起来。最后，我们计划使用新型的遗传学工具来测试这些大脑法规和电路的因果作用（AIM 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内暂时使每个大脑区域失活。这将使我们能够确定每个大脑区域参与的必要时间和时间过程。最后，我们将操纵每个大脑区域内神经元的解剖学定义和计算鉴定的子集的活性，以确定特定的亚群是否在行为中起因果作用。通过整合广泛的尖端实验和计算工具，并组装一个具有多学科专业知识的协作团队，我们希望改变对基本记忆引导的感知决策的神经元的理解。