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: 10390033
• 负责人: William M Sheeran
• 金额: $ 3.91万
• 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/10390033
• 关键词: Alzheimer' s Disease; Area; Base Pairing; Brain; Brain region; Calcium; Cognitive Therapy; Communication; Data; Disease; Dissection; Distant; Elements; Emotional; Ensure; Family; Foundations; Friends; Future; Goals; Hippocampus (Brain); Human; Impaired cognition; Impairment; Knowledge; Label; Laboratories; Life; 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; Sum; System; Technology; Testing; Time; Training; Translating; Translations; Work; career; cellular imaging; clinical translation; comparative; daily functioning; experience; frontal lobe; in vivo; in vivo calcium imaging; long term memory; memory acquisition; memory consolidation; memory encoding; memory process; memory recall; memory recognition; mouse model; neural circuit; neuromechanism; neuropsychiatric disorder; neuropsychiatry; neurotechnology; neurotransmission; novel; post-traumatic stress; prairie vole; preference; prevent; psychological distress; recruit; relating to nervous system; 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 社交记忆对于日常功能至关重要，但在许多神经精神疾病中受到损害， 包括阿尔茨海默氏病和创伤后应激障碍。有效疗法的社会疗法死亡 记忆缺陷需要严格研究控制社会记忆动态的神经回路机制。 在小鼠中最近的工作表明，腹侧海马区域CA1（VCA1）和培养基中的神经元合成 前额叶皮层（MPFC）编码社会互动的各个方面，包括社会的身份 同种。此外，从VCA1到MPFC的项目中完整的沟通对于短期社会至关重要 识别记忆和神经精神疾病的鼠标模型，社交记忆显示受损 相应的网络在此途径中定义。这些发现与长长的规范模型相结合 海马将内存表示的关键组成部分转移到正面的术语内存 长期合并的皮质区域。但是，长期合并社会的机制 记忆，例如社会记忆是否遵守这种海马皮质转移模型，在很大程度上仍然是 未经评价。这种辩护的主要原因是社会记忆的高度短暂的本质 实验室啮齿动物阻止有意义地研究长期召回的努力。 这是该提案的目的是测试海马皮层记忆转移是否持续 社交记忆的合并，使用一对长期社交记忆的新型模型，搭配的草原田鼠。 大草原像人类一样，形成一夫一妻，基于交配的成对键。这些债券需要稳定， 长期维护的伴侣的情感上有明显的记忆；因此，这个项目将利用对 作为持久和情感上显着的社交记忆的代理。 AIM 1将确定必要的 VCA1，MPFC和VCA1至MPFC项目中的完整神经元信号传导 通过可逆的化学遗传抑制每个电路成分的采集和长期回忆。目标2 将检查VCA1中的神经元动态及其对参与组成和长期涉及的MPFC的项目 通过体内钙成像来回顾成对伴侣的记忆。 总而言之，该建议将扩大我们对情感显着社会的基本理解 形成记忆并存储，以使大脑中的遥远回忆。这项工作还将提供适用的 对他作为神经精神病学家未来职业的宝贵培训，专注于翻译基础知识 从系统神经科学到新颖的，高度精确的认知功能障碍疗法。