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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。

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目总结