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.

海马神经活动的表征 积累和决策 项目摘要/摘要 在不断变化的环境中，积累和评估证据的能力对于最佳 决策。海马被认为体现了认知图，并经过了很好的研究 导航和觅食任务。但是，尚不清楚海马在证据时的行为 决策必须随着时间的流逝而积累。我们将使用钙成像来测量 在小鼠中，数百个CA1神经元与嘈杂的视觉提示导航的小鼠中 迷宫末端的正确决定的动物（左或右转弯）。我们的第一个目标是建造 在此任务中，CA1神经活动的综合模型可以解释 证据和地点，可能与其他感知和行为变量多样化。有希望的初步 证据表明，CA1神经元编码的空间信息是由证据数量调节的 那已经收到了。除了单细胞活性外，证据还表明CA1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是否 CA1种群活动的顺序性质具有超出单个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是否形成 作为CA1人口活动的因果结果。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，以调查大型活动的协调活动 除了结合细胞分辨率光遗传激活/抑制外，神经元的群体种群 与2光子钙成像同时。这些实验将共同确立 在以前未研究的情况下海马。除了基础科学研究的重要性之外， 了解证据积累和决策背后的神经过程也很重要 对精神病和神经系统疾病的管理的影响，例如强迫症 这些功能中断的障碍，成瘾或注意力缺陷多动障碍。