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 正确地导航我们的日常生活需要明智地使用我们有限的认知资源，以产生一个 期望的结果。这种能力，被称为认知控制，已被证明在人类严重依赖 前额叶皮层的大脑区域，包括前扣带皮层，这与努力有关。 决策和业绩监测。海马体也与认知控制有关 特别是当任务依赖于先前的经验时。海马神经元的单单位记录 揭示了一个协调的认知控制信号，预测认知控制行为。的机理 认知控制，以及大脑区域对它的贡献仍然不清楚，但前扣带是最重要的 可能的候选人。目的1将探讨前额叶认知控制表征通过使用在体单光子 钙成像记录大鼠执行任务时前扣带回皮质（ACC）内的神经元群体 主动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，就像海马体中的信号一样。是否有类似的信号 存在并不排除它参与认知控制。因此，目标2将选择性地抑制ACC 在认知控制任务中使用抑制性化学遗传学（DREADDs）来测试各种过程中的必要性。 行为阶段我们还将记录海马CA 1区的群体神经元活动， 操作，以评估扣带回失活对海马认知控制信号的影响。 这项研究的结果将揭示认知控制是如何在ACC中表现的，以及这种活动如何影响 海马认知控制，以及提供了一个解释如何影响执行功能障碍的基础， 功能障碍（如精神分裂症和额颞叶痴呆症）影响大脑。这项工作推动了《联合国千年宣言》的目标1。 国家心理健康研究所-定义复杂行为背后的大脑机制。只有 研究认知控制是如何在多个不同的大脑区域中表现和协调的， 开始构建对复杂大脑功能和精神疾病的整体理解。