Perturbations and Behavior

项目摘要：项目1，扰动和行为 工作记忆，即在脑海中暂时记住多个信息以进行操作的能力，是 几乎是所有认知能力的核心。这一多组分研究项目旨在全面 剖析这种能力在多个大脑区域的神经回路机制。的各个部分 项目概念上的一致性，部分是因为它们都涉及到训练成执行一种类型的 基于感官证据的逐渐积累的决策任务，因此依赖于 工作记忆。工作记忆和决策的神经关联分布在 广泛的皮质和皮质下区域，但这些区域中哪些真正导致 这些进程--最重要的是，它们的贡献可能是什么--仍然遥不可及。 一个重要的障碍是这些进程可以快速发展(例如，从加载 将物品放入工作存储器中、将其保存在存储器中、再将其取回)， 例如抑制性光遗传分子，可以足够快地开启和关闭，以区分 不同的阶段。该项目将使用光遗传失活与这套密切相关的 头部固定啮齿动物的工作记忆和决策任务。这些任务是高度服从的 定量行为分析。这些特点将使系统和全面的定量调查成为可能 对工作记忆和决策的因果贡献的一组非常大的区域 背侧皮质、更深的皮质和目标皮质下区域，包括小脑、腹侧 被盖区、海马体和纹状体。其他实验将研究 不同的基因定义的细胞类型，在目标大脑区域。总而言之，这些实验是 有望提供有关大脑中特定神经元如何相互作用的详细信息 工作记忆和决策，增加对大脑认知基础的了解。

Project Summary: Project 1, Perturbations and Behavior Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. This multi-component research project aims to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. The individual parts of the project cohere conceptually, in part, because they all involve rodents trained to perform a type of decision-making task that is based on the gradual accumulation of sensory evidence and thus relies on working memory. Neural correlates of working memory and decision-making are distributed across a very wide range of cortical and subcortical regions, but a complete listing of which of these regions actually cause these processes—and most importantly, what the nature of their contribution might be—remains out of reach. A significant obstacle has been that these processes can evolve rapidly (for example, going from loading an item into working memory, to holding it in memory, to retrieving it) and it is only recently that inactivation tools, such as inhibitory optogenetic molecules, could be turned on and off fast enough to distinguish between different phases. This project will use optogenetic inactivation in combination with this set of closely related working memory and decision-making tasks for the head-fixed rodent. The tasks are amenable to highly quantitative behavioral analysis. These features will allow a systematic and comprehensive quantitative probe of the causal contribution to working memory and decision-making of a very large set of regions across the dorsal cortex, deeper cortices, and targeted subcortical regions, including the cerebellum, the ventral tegmental area, the hippocampus, and the striatum. Other experiments will study the causal contributions of different genetically defined cell types, in targeted brain regions. Taken together, these experiments are expected to provide detailed information about how the interaction of particular neurons in the brain produces working memory and decisions, increasing knowledge about the brain basis of cognition.