Investigation of Anterior Cingulate Cortex Contributions to Hippocampal Cognitive Control

前扣带皮层对海马认知控制的贡献研究

• 批准号: 10827013
• 负责人: Garrett Blair
• 金额: $ 6.91万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-11-01 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10827013
• 关键词: Address; Affect; Animal Experimentation; Animals; Anterior; Behavior; Behavior Control; Behavioral; Brain; Brain region; Calcium; Categories; Cognitive; Complex; Conflict (Psychology); Decision Making; Distal; Distant; Electrophysiology (science); Frontotemporal Dementia; Functional disorder; Future; Genetic; Goals; Hippocampal Formation; Hippocampus; Human; Image; Inherited; Investigation; Learning; Lesion; Limbic System; Maps; Medial; Mediating; Memory; Mental disorders; Monitor; Mus; National Institute of Mental Health; Neurons; Outcome; Performance; Phase; Photons; Population; Population Dynamics; Positioning Attribute; Prefrontal Cortex; Process; Pyramidal Cells; Rattus; Research; Resources; Retrieval; Role; Rotation; Schizophrenia; Sensory; Shock; Signal Transduction; Source; Stimulus; Strategic Planning; Synapses; Testing; Time; Training; Work; cingulate cortex; cognitive control; designer receptors exclusively activated by designer drugs; entorhinal cortex; excitatory neuron; executive function; experience; experimental study; flexibility; in vivo; in vivo calcium imaging; insight; meetings; memory retrieval; neural

Project Abstract Properly navigating our daily lives necessitates the judicious use of our limited cognitive resources to yield a desired outcome. This ability, known as cognitive control, has been demonstrated in humans to depend heavily on brain regions in the prefrontal cortex, including the anterior cingulate cortex, which is involved in effortful decision making and performance monitoring. The hippocampus has also been implicated in cognitive control function, particularly when the task depends on prior experience. Single-unit recordings of hippocampal neurons have revealed a coordinated cognitive control signal that predicts cognitive control behavior. The mechanism of cognitive control, and which brain regions contribute to it remains unclear, but the anterior cingulate is the most likely candidate. Aim 1 will explore prefrontal cognitive control representations by using in-vivo single photon calcium imaging to record populations of neurons within the anterior cingulate cortex (ACC) while rats perform an active place avoidance task. This is a navigation based cognitive control task that will enable us to determine if ACC also expresses a cognitive control signal, like in the signal in hippocampus. Whether or not a similar signal exists does not preclude its involvement in cognitive control. Therefore Aim 2 will selectively inactivate ACC using inhibitory chemogenetics (DREADDs) during the cognitive control task to test for necessity during various behavioral phases. We will also record population neuronal activity from hippocampus CA1 during the manipulations to evaluate the influence of cingulate inactivation on the hippocampal cognitive control signal. Results from this research will reveal how cognitive control is represented in ACC and how this activity influences hippocampal cognitive control, as well as provide a basis for interpreting how dysfunction that affects executive function (such as schizophrenia and frontotemporal dementia) impact the brain. This work furthers Goal 1 of the National Institute of Mental Health – defining the brain mechanisms underlying complex behaviors. Only by addressing how cognitive control is represented and coordinated across multiple diverse brain regions can we begin to construct a wholistic understanding of complex brain functions and mental illness.

项目摘要 正确地驾驭我们的日常生活需要明智地使用我们有限的认知资源来产生 期望的结果。这种被称为认知控制的能力已经在人类身上被证明严重依赖于 在前额叶皮质的大脑区域，包括前扣带回皮质，它参与了努力 决策和绩效监控。海马体也与认知控制有关。 功能，特别是当任务依赖于先前的经验时。海马神经元的单位记录 揭示了一种预测认知控制行为的协调认知控制信号。它的作用机制 认知控制，以及大脑的哪些区域参与了认知控制，目前尚不清楚，但前扣带回是最重要的 可能的候选人。目标1将使用活体单光子来探索前额叶认知控制表征 钙成像记录大鼠前扣带回(ACC)内神经元的数量 主动的位置回避任务。这是一个基于导航的认知控制任务，它将使我们能够确定 如果ACC也表达认知控制信号，就像在海马体中的信号一样。不管是不是类似的信号 EXISTS并不排除它参与认知控制。因此，目标2将选择性地停用访问权限 在认知控制任务中使用抑制性化学遗传学(DREADD)来测试在不同的 行为阶段。我们还将记录海马区CA1区的群体神经元活动 评估扣带回失活对海马区认知控制信号的影响。 这项研究的结果将揭示认知控制在ACC中是如何表现的，以及这种活动是如何影响的 海马区的认知控制，以及为解释功能障碍如何影响执行提供了基础 功能(如精神分裂症和额颞痴呆)会影响大脑。这项工作进一步推进了 国家心理健康研究所--定义复杂行为背后的大脑机制。仅限于 解决认知控制如何在多个不同的大脑区域表现和协调的问题上，我们可以 开始对复杂的大脑功能和精神疾病建立一个整体的理解。