Characterization of Hippocampal Neural Activity in Evidence Accumulation and Decision-Making

海马神经活动在证据积累和决策中的表征

• 批准号: 9760519
• 负责人: Horng-An Edward Nieh
• 金额: $ 6.16万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9760519
• 关键词: Animals; Attention deficit hyperactivity disorder; Basic Science; Behavior; Behavioral; Belief; Biophysics; Calcium; Cells; Code; Cognitive; Complex; Control Animal; Cues; Decision Making; Dependence; Disease; Environment; Fire - disasters; Frequencies; Future; Goals; Head; Hippocampus (Brain); Image; Individual; Left; Maintenance; Maps; Measures; Memory; Mental disorders; Modeling; Mus; Nature; Neurons; Obsessive-Compulsive Disorder; Odors; Population; Process; Research; Resolution; Rewards; Rodent; Role; Running; Sensory; Side; Time; Visual; Work; addiction; biophysical properties; experience; experimental study; nervous system disorder; neural circuit; optogenetics; place fields; relating to nervous system; stem; tool; two-photon; virtual; virtual reality; way finding

Characterization of Hippocampal Neural Activity in Evidence Accumulation and Decision-Making Project Summary/Abstract In an ever-changing environment, the ability to accumulate and evaluate evidence is crucial for optimal decision-making. The hippocampus is thought to embody a cognitive map and has been well-studied in navigation and foraging tasks. However, it is unknown how the hippocampus behaves when evidence for decision-making must be accumulated over time. We will use calcium imaging to measure neural activity from hundreds of CA1 neurons simultaneously in mice navigating a virtual T-maze with noisy visual cues that inform the animal of the correct decision (left or right turn) at the end of the maze. Our first aim will be to build a comprehensive model of CA1 neural activity during this task that can account for the primary variables of evidence and place, possibly multiplexed with other perceptual and behavioral variables. Promising preliminary evidence suggests that CA1 neurons encode spatial information that is modulated by the amount of evidence that has been received. In addition to single cell activity, evidence also suggests that CA1 neurons can organize into multiple sequences in the same environment. Our second aim is to evaluate whether the sequential nature of CA1 population activity holds task-relevant information beyond individual neuron activity. Our third aim is to investigate the biophysical underpinnings of these sequences and whether their formation takes place as a causal result of population activity in the CA1. To achieve these goals, we will utilize rodent virtual reality behavior, multidimensional analysis tools to investigate the coordinated activity of large populations of neurons, in addition to combining cellular-resolution optogenetic activation/inhibition simultaneously with 2-photon calcium imaging. Together, these experiments will establish a role for the hippocampus in a previously unstudied context. Beyond the significance for basic science research, understanding the neural processes behind evidence accumulation and decision-making also has important implications in the management of psychiatric and neurological disorders, such as obsessive-compulsive disorder, addiction, or attention deficit hyperactivity disorder, in which these functions are disrupted.

海马神经活动的证据表征 积累与决策 项目总结/摘要 在一个不断变化的环境中，积累和评估证据的能力对于优化 决策的海马体被认为是认知地图的具体体现，并在 导航和觅食任务。然而，海马体在有证据表明 决策必须随着时间的推移而积累。我们将使用钙成像来测量神经活动， 数百个CA 1神经元同时在小鼠中导航虚拟T迷宫， 在迷宫的尽头做出正确决定（左转或右转）的动物。我们的首要目标是建立一个 该任务期间CA 1神经活动的综合模型，可以解释以下主要变量 证据和地点，可能与其他感知和行为变量复用。有希望的初步 有证据表明，CA 1神经元编码的空间信息受到证据量的调节 已经收到了。除了单细胞活动，证据还表明CA 1神经元可以 在同一环境中组织成多个序列。我们的第二个目标是评估 CA 1群体活动的顺序性质保持了超出个体神经元活动的任务相关信息。 我们的第三个目标是研究这些序列的生物物理基础，以及它们的形成是否 是CA 1中种群活动的因果结果。为了实现这些目标，我们将利用啮齿动物 虚拟现实行为，多维分析工具，调查协调活动的大 除了结合细胞分辨率光遗传学激活/抑制之外， 同时进行双光子钙成像。总之，这些实验将确立一个角色， 海马在以前未研究的情况下。除了对基础科学研究的意义之外， 了解证据积累和决策背后的神经过程也很重要， 精神和神经系统疾病，如强迫症， 障碍、成瘾或注意缺陷多动障碍，其中这些功能被破坏。