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

基本信息

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
项目类别：
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

项目摘要

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概要/摘要在不断变化的环境中，积累和评估证据的能力对于实现最佳目标至关重要。决策。海马体被认为体现了认知地图，并已在以下领域得到充分研究：导航和觅食任务。然而，当有证据表明海马体的行为方式是未知的。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小鼠体内数百个 CA1 神经元同时在虚拟 T 迷宫中导航，并通过嘈杂的视觉线索提供信息迷宫尽头做出正确决定（左转或右转）的动物。我们的首要目标是建立一个在此任务期间 CA1 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。初步有希望有证据表明 CA1 神经元编码受证据数量调节的空间信息已收到。除了单细胞活动外，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 群体活动的顺序性质包含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这是 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，多维分析工具来研究大型协调活动除了结合细胞分辨率光遗传学激活/抑制之外，神经元群体同时进行 2 光子钙成像。总之，这些实验将为海马体处于先前未研究过的环境中。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对治疗精神和神经疾病（例如强迫症）的影响障碍、成瘾或注意力缺陷多动障碍，其中这些功能被破坏。