Mechanisms of neural circuit dynamics in working memory and decision-making

工作记忆和决策中的神经回路动力学机制

• 批准号: 10705962
• 负责人: Carlos D Brody
• 金额: $ 468.67万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-08 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705962
• 关键词: Address; Alzheimer' s Disease; Anatomy; Animals; Architecture; Area; Arousal; Attention deficit hyperactivity disorder; BRAIN initiative; Basic Science; Behavior; Behavioral; Behavioral Paradigm; Biological Assay; Bipolar Depression; Brain; Brain region; Cognitive; Computer Models; Data; Decision Making; Dementia; Development; Electron Microscopy; Electrophysiology (science); Etiology; Exhibits; Family; Geometry; Goals; Hippocampus; Hunger; Image; Individual; Joints; Link; Maps; Mental disorders; Methods; Modeling; Modernization; Mus; Neocortex; Neurons; Neurosciences; Performance; Physiological; Positioning Attribute; Research; Research Personnel; Resolution; Rodent; Role; Running; Schizophrenia; Series; Short-Term Memory; Side; Silicon; Statistical Methods; Structure; System; Task Performances; Technology; Testing; Therapeutic; Thirst; Time; Transmission Electron Microscopy; Variant; Work; autism spectrum disorder; cognitive ability; cognitive process; computer studies; experimental study; member; neocortical; neural; neural circuit; neuromechanism; next generation; novel; operation; population based; programs; scaffold; virtual reality

Project Summary/Abstract: Overall The overarching goal of this U19 program is to determine how neural computations across brain regions produce two core cognitive processes, working memory and decision-making, and thus to derive fundamental principles of brain function. This renewal application proposes to pursue powerful new themes that emerged from our previous work and to broaden our scope substantially. To do so, the eight PIs plan a tightly integrated set of experimental and computational studies of mice doing the accumulating towers task—in which they must remember how many towers flash on each side as they run down a maze in virtual reality—and related tasks. The first theme arises from the finding that neurons across the brain encode task variables and are necessary for task performance. Almost all of these areas exhibit sequential activity, in which neurons are active at different times in the task and, together, tile the trial duration. Project 1 will identify the task features that drive sequential activity, use cooling to identify neural circuits that generate sequential activity, and elucidate its anatomical basis by combining transmission electron microscopy and computational modeling. A second theme is that manifold inference methods, applied to large-scale hippocampal recordings in our task, reveal the geometry of a joint neural representation for an external variable (position) and an internal, cognitive variable (accumulated evidence). Project 2 will extend our work on the geometry of neural representations to other brain regions. We will examine how geometries and representations in these regions interact with each other, and we will develop models to explain how the observed neural manifolds arise. A third theme, fueled by our development of statistical methods to infer internal brain states, is that animals’ brains occupy qualitatively different states from trial to trial during the same task block. Our data suggests that behavior in each state requires different neural structures and circuits—in the same animal and the same trial block. Project 3 will use multi-region recordings and perturbations to investigate whether states are local to subcircuits versus global across the brain, extend our behavioral inference methods to neural data, and examine to what extent our inferred states are linked to internal states of arousal, thirst, and hunger. Elucidating how multiple circuits performing local computations combine into a brain in action is the goal of Projects 4 and 5. Project 4 will probe functional interactions in multi-region recordings, including very large-scale simultaneous electrophysiological recordings with next-generation silicon probes; and through targeted experiments will test two hypotheses of how subcortical regions interact with neocortex. Project 5 will generate a set of mechanistic models that instantiate specific hypothesized roles of different brain regions. These local models will be combined into a single multi-regional model, informed by data from all projects, that will enable us to dissect the roles of individual regions and their interactions in performance of the many variants of our decision-making task.

项目摘要/摘要：总体