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

摘要 大脑的认知功能允许高等动物以复杂和适应性的方式与世界互动 礼貌。例如，动物利用过去的经验来开发规则和上下文的内部模型 塑造后续决策。这些认知过程在许多毁灭性的心理健康中被打乱 精神错乱。认知神经科学的传统实验已经确定了认知与 过程和行为输出或神经事件。然而，揭开原因一直是一项挑战。 认知过程从神经生物学的基本构件中产生的机制 计算：分子、细胞、突触和电路。究其原因，很大程度上是因为 将神经科学中新兴的机械论方法与研究认知过程的范例相结合。 在这里，我们的目标是通过开发一项研究计划来确定 认知过程与结构--细胞类型、连通性--和功能--时空活动 神经群体中的模式-神经回路的模式。我们最近设计了一个虚拟现实系统，用于鼠标和 开发了训练小鼠在虚拟环境中导航时执行复杂的认知任务的方法 环境。此外，我们开发了神经生理学和计算工具，确定了相关因素 在神经元群体的活动模式中的认知过程。我们将利用这个基金会建立一个 机械认知神经科学研究计划。首先，我们将开发一份认知功能细胞类型的图谱 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 在灵活的决策任务期间。第二，我们将建立基于单神经元光遗传学的方法 以揭示认知行为过程中识别出的细胞之间的联系。第三，我们将使用钙成像来 “阅读”认知任务中的神经活动模式，然后使用 图案化的光遗传学来测试充分性和必要性。我们将研究这些结构和功能特性 在局部神经元群体(微回路)和跨脑区(中回路)。这项工作将扩大 机械认知神经科学的新兴领域，并制定一个新的研究计划，以实现以下目标 从核心生物学成分和机制的角度定义认知和心理健康。

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.