Mechanisms of neural circuit dynamics in working memory anddecision-making

项目摘要 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。最近的技术进步开启了一种前所未有的 有机会全面剖析这种能力在多个大脑中的神经回路机制 区域。要研究的任务是一种常见的决策形式，它是基于渐进的 感官证据的积累，因此依赖于工作记忆。一组顶尖的专家建议 使用包括虚拟现实在内的最新技术来研究这种行为的神经基础， 高通量自动行为训练，对表现良好的啮齿动物进行大规模细胞分辨率成像， 操纵特定脑区和细胞类型的神经活动，并自动解剖 重建。特别是，研究人员将确定做出这一决定所需的关键大脑区域 通过光遗传学技术在整个背部进行系统的、时间上特定的失活任务 大脑皮层和关键皮质下区域，并使用定量模型拟合来评估效果。他们将使用 最新的双光子钙成像方法和电生理学来表征信息 在任务过程中，这些大脑区域内的许多单个神经元都会流动。此外，他们还将使用 大脑内部和跨大脑的尖端解剖重建和新的功能连接方法 区域，以评估这些生理特征神经元之间的相互作用。的长期目标是 这个项目是为了达到一个完整的，全脑的理解细胞和电路的机制 与工作记忆相关的活动动力学。最后，他们将使用复杂的计算方法来 将这一新的理解融入到现实的电路模型中，以支持紧密集成的 以模型为导向的实验设计过程，其中模型提供的信息最丰富 然后反馈实验及其结果，以提高模型的保真度。这一进程预计将 制作认知过程的最准确和最详细的多脑区域生物物理回路模型 存在着。此外，拟议的研究将使研究人员能够生成和测试各种 关于证据积累、工作记忆和决策的神经基础的假设。 综上所述，这些成就将代表着朝着机械地理解如何 大脑与信息打交道。

Project Summary Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. Recent technical advances have opened an unprecedented opportunity to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. The task to be studied is a common form of decision-making that is based on the gradual accumulation of sensory evidence and thus relies on working memory. A team of leading experts propose to investigate the neural basis of this behavior using the latest techniques, including virtual reality, high-throughput automated behavioral training, large-scale cellular-resolution imaging in behaving rodents, manipulation of neural activity in specific brain areas and cell types, and automated anatomical reconstruction. In particular, the researchers will identify key brain regions that are required for this decision task through systematic, temporally specific inactivations via optogenetics technology, across all of dorsal cortex and in key subcortical areas, and use quantitative model-fitting to evaluate the effects. They will use state-of-the-art two-photon calcium imaging methods and electrophysiology to characterize the information flow in many individual neurons within these brain areas during the task. In addition, they will use cutting-edge anatomical reconstructions and new functional connectivity methods, within and across brain regions, to evaluate the interactions of these physiologically characterized neurons. The long-term goal of this project is to arrive at a complete, brain-wide understanding of the cellular and circuit mechanisms of activity dynamics related to working memory. Finally, they will use sophisticated computational methods to incorporate this new understanding into a realistic circuit model that will support a tightly integrated process of model-guided experimental design, in which the model suggests the most informative experiments and their results are then fed back to improve the model’s fidelity. This process is expected to produce the most accurate and detailed multi-brain-region biophysical circuit model of a cognitive process in existence. In addition, the proposed research will enable researchers to generate and test a variety of hypotheses about the neural basis of evidence accumulation, working memory, and decision-making. Taken together, these achievements will represent a crucial step toward a mechanistic understanding of how the brain works with information.