Toward mechanistic cognitive neuroscience: cell types, connectivity, and patterned perturbations

迈向机械认知神经科学：细胞类型、连接性和模式扰动

基本信息

批准号：
10468896
负责人：
Christopher D Harvey
金额：
$ 118.65万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-07-31
项目状态：
未结题

项目摘要

Summary The cognitive functions of the brain allow higher animals to interact with the world in complex and adaptive manners. For example, animals use past experiences to develop internal models of rules and contexts that shape subsequent decisions. These cognitive processes are disrupted in many devastating mental health disorders. Traditional experiments in cognitive neuroscience have identified correlations between cognitive processes and behavioral outputs or neural events. However, it has been challenging to uncover the causal mechanisms by which cognitive processes emerge from the basic building blocks of neurobiological computations: molecules, cells, synapses, and circuits. The reason is, in large part, because it has been difficult to combine emerging mechanistic approaches in neuroscience with paradigms to study cognitive processes. Here we aim to overcome these challenges by developing a research program to identify causal links between cognitive processes and the structure – cell types and connectivity – and function – spatiotemporal activity patterns in neural populations – of neural circuits. We recently devised a virtual reality system for mice and developed methods to train mice to perform complex, cognitive tasks as they navigate through virtual environments. Further, we developed neurophysiological and computational tools that have identified correlates of cognitive processes in the activity patterns in population of neurons. We will use this foundation to establish a research program for mechanistic cognitive neuroscience. First, we will develop an atlas of cell types in cognitive brain regions, use viral tools to label these cell types, and then study the functional roles of these cell types during flexible decision-making tasks. Second, we will establish methods based on single-neuron optogenetics to reveal connectivity between identified cells during cognitive behaviors. Third, we will use calcium imaging to ‘read’ patterns of neural activity during cognitive tasks and will then ‘write’ and ‘erase’ these patterns using patterned optogenetics to test sufficiency and necessity. We will study these structural and functional properties in local populations of neurons (microcircuits) and across brain areas (mesocircuits). This work will expand the emerging field of mechanistic cognitive neuroscience and develop a new research program toward the goal of defining cognition and mental health in terms of core biological components and mechanisms.

概括大脑的认知功能使高等动物在复杂和适应性的方面与世界互动举止。例如，动物利用过去的经验来开发内部模型的规则和环境模型形状随后的决定。这些认知过程在许多毁灭性的心理健康中被破坏疾病。认知神经科学的传统实验已经确定了认知之间的相关性过程和行为输出或神经事件。但是，发现因果关系受到挑战认知过程从神经生物学的基本构建基础中出现的机制计算：分子，细胞，突触和圆圈。原因很大程度上是因为很难将神经科学中的新兴机械方法与研究认知过程相结合。在这里，我们旨在通过制定研究计划来确定因果关系，以克服这些挑战认知过程和结构 - 细胞类型和连通性 - 以及功能 - 时空活动神经封锁的神经吞噬模式。我们最近为小鼠设计了一个虚拟现实系统开发了训练小鼠在通过虚拟导航时执行复杂，认知任务的方法环境。此外，我们开发了鉴定已确定相关性的神经生理学和计算工具神经元种群活动模式中认知过程的认知过程。我们将使用这个基础来建立一个机械认知神经科学研究计划。首先，我们将在认知中开发细胞类型的地图集大脑区域，使用病毒工具标记这些细胞类型，然后研究这些细胞类型的功能作用在灵活的决策任务中。其次，我们将基于单神经元的光遗传学建立方法在认知行为过程中揭示已识别细胞之间的连通性。第三，我们将使用钙成像认知任务期间神经活动的“读取”模式，然后将“写”和“擦除”这些模式图案化的光遗传学测试充足和必要。我们将研究这些结构和功能特性在局部神经元（微电路）和跨大脑区域（中环）中。这项工作将扩大机械认知神经科学的新兴领域，并制定了新的研究计划以实现根据核心生物学成分和机制定义认知和心理健康。