Investigating the role of hippocampocortical circuitry in long term social memory.

研究海马皮质回路在长期社会记忆中的作用。

• 批准号: 10548736
• 负责人: William M Sheeran
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548736
• 关键词: Alzheimer' s Disease; Area; Base Pairing; Brain; Brain region; Cognitive Therapy; Communication; Data; Disease; Dissection; Distant; Elements; Emotional; Ensure; Family; Friends; Future; Genetic; Goals; Hippocampus; Human; Impaired cognition; Impairment; Knowledge; Label; Laboratories; Longitudinal Studies; Maintenance; Medial; Memory; Memory impairment; Methods; Microtus; Modeling; Mus; Nature; Neurons; Neurosciences; Pair Bond; Partner in relationship; Pathway interactions; Persons; Physicians; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Proxy; Rattus; Rodent; Rodent Model; Role; Signal Transduction; Social Interaction; Societies; System; Technology; Testing; Time; Training; Translating; Translations; Work; career; cellular imaging; clinical translation; comparative; daily functioning; experience; frontal lobe; in vivo calcium imaging; long term memory; member; memory acquisition; memory consolidation; memory encoding; memory process; memory recall; memory recognition; mouse model; neural; neural circuit; neuromechanism; neuropsychiatric disorder; neuropsychiatry; neurotechnology; neurotransmission; novel; prairie vole; preference; prevent; psychological distress; recruit; social; therapeutically effective

Project Summary Social memory is critical for daily functioning but becomes impaired in many neuropsychiatric disorders, including Alzheimer disease and post-traumatic stress disorder. The dearth of effective therapeutics for social memory deficits demands rigorous study of the neural circuit mechanisms governing social memory dynamics. Recent work in mice has shown that neuronal ensembles in ventral hippocampal area CA1 (vCA1) and medial prefrontal cortex (mPFC) encode various aspects of social interaction, including the identity of a social conspecific. Moreover, intact communication in projections from vCA1 to mPFC is critical for short-term social recognition memory, and mouse models of neuropsychiatric disorders with impaired social memory display corresponding network deficits in this pathway. These findings are well-aligned with a canonical model of long- term memory in which the hippocampus transfers a critical component of a memory’s representation to frontal cortical areas for long-term consolidation. However, mechanisms underlying long-term consolidation of social memories, such as whether social memories abide by this hippocampocortical transfer model, remain largely uninvestigated. A major reason for this deficit is the highly fleeting nature of social memories in common laboratory rodents preventing meaningful efforts to study long-term recall. Thus, the goal of this proposal is to test whether hippocampocortical memory transfer underlies lasting social memory consolidation using a novel model of long-term social memory in pair bonded prairie voles. Prairie voles, like humans, form monogamous, mating-based pair bonds. These bonds require stable, emotionally salient memory of the partner for long-term maintenance; this project will thus leverage pair bonding as a proxy for lasting and emotionally salient social memory. Aim 1 will determine the necessity of intact neuronal signaling in vCA1, mPFC, and vCA1-to-mPFC projections in prairie vole pair bond memory acquisition and long-term recall through reversible chemogenetic inhibition of each circuit component. Aim 2 will examine neuronal dynamics in vCA1 and its projections to mPFC involved in the formation and long-term recall of the memory of a pair bonded partner through in vivo calcium imaging. In sum, this proposal will expand our fundamental understanding of how emotionally salient social memories are formed and stored for distant recall in the brain. This work will also provide the applicant with invaluable training for his future career as a neuropsychiatrist focused on translating foundational knowledge from systems neuroscience into novel, highly precise therapies for cognitive dysfunction.

项目摘要 社会记忆对日常功能至关重要，但在许多神经精神障碍中会受到损害， 包括阿尔茨海默病和创伤后应激障碍。缺乏有效的社会治疗方法 记忆缺陷需要对支配社会记忆动态的神经回路机制进行严格的研究。 最近对小鼠的研究表明，神经元在腹侧海马CA1区(VCA1)和内侧 前额叶皮质(MPFC)编码社会互动的各个方面，包括一个社会的身份 同种的。此外，从vCA1到mPFC的预测中的完整沟通对于短期社交网络至关重要 识别记忆和社会记忆显示受损的神经精神障碍的小鼠模型 这条通路中相应的网络缺陷。这些发现很好地符合一个典型的长期模型。 一种术语记忆，海马体将记忆表征的关键成分转移到额叶 长期巩固的大脑皮层区域。然而，长期巩固社会基础的机制 记忆，例如社会记忆是否遵守这种海马皮层转移模型，在很大程度上仍然存在 未经调查。造成这种差距的一个主要原因是共同的社会记忆的高度转瞬即逝 实验室啮齿动物阻止有意义的努力来研究长期记忆。 因此，这项提议的目标是测试海马区大脑皮层记忆转移是否建立在 在配对结合的草原田鼠中使用一种新的长期社会记忆模型来巩固社会记忆。 草原田鼠和人类一样，形成以交配为基础的一夫一妻制的伴侣关系。这些债券需要稳定、 在情感上突出对合作伙伴的记忆，用于长期维护；因此，该项目将利用Pair 作为持久的和情感上突出的社会记忆的代言人。目标1将决定是否有必要 草原田鼠对键记忆中vCA1、mPFC和vCA1-mPFC投射中的完整神经元信号 通过对每个电路元件的可逆化成抑制获得和长期回忆。目标2 我将研究vCA1中的神经元动力学及其向mPFC的投射参与形成和长期 通过体内钙成像回忆一对结合在一起的伴侣的记忆。 总而言之，这项建议将扩大我们对社会情绪如何突出的基本理解 记忆在大脑中形成并储存起来，供遥远的回忆之用。这项工作还将为申请人提供 作为一名专注于翻译基础知识的神经精神病学家，为他未来的职业生涯提供了宝贵的培训 从系统神经科学到认知障碍的新的、高度精确的治疗方法。