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 社交记忆对日常功能至关重要，但在许多神经精神疾病中会受损， 包括阿尔茨海默病和创伤后应激障碍。缺乏有效的治疗方法， 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。 最近在小鼠中的研究表明，腹侧海马CA 1区（vCA 1）和内侧海马CA 2区（vCA 1）的神经元集合体 前额叶皮层（mPFC）编码社会互动的各个方面，包括社会成员的身份。 同种的此外，从vCA 1到mPFC的预测中的完整通信对于短期社会影响至关重要。 识别记忆和具有受损社会记忆显示的神经精神障碍的小鼠模型 相应的网络缺陷。这些发现与长期的典型模型一致， 海马体将记忆表征的关键成分转移到额叶的一种术语记忆 长期巩固的皮质区。然而，社会长期巩固的机制 记忆，比如社交记忆是否遵循这种大脑皮层转移模型，在很大程度上仍然存在， 未经调查这种缺陷的一个主要原因是社会记忆的共同点非常短暂 实验室啮齿动物阻碍了长期记忆研究的有意义的努力。 因此，本研究的目的是测试大脑皮层记忆转移是否是持久记忆的基础。 社会记忆巩固使用一种新的模式，长期社会记忆的配对结合草原田鼠。 草原田鼠，像人类一样，形成一夫一妻制，交配为基础的配对债券。这些债券需要稳定， 情感上突出的记忆的合作伙伴长期维护;这个项目将因此利用对 作为持久和情感上突出的社会记忆的代表。目标1将决定 草原田鼠成对键记忆中vCA 1、mPFC和vCA 1-mPFC投射中的完整神经元信号传导 通过每个回路组件的可逆化学发生抑制获得和长期回忆。目的2 将研究vCA 1的神经元动力学及其对mPFC的预测， 通过体内钙成像回忆成对结合的伴侣的记忆。 总之，这个提议将扩展我们对情绪突出的社会性如何的基本理解。 记忆在大脑中形成并储存以供遥远的回忆。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， 从系统神经科学到新型的、高度精确的认知功能障碍疗法。