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Reorganization of cortical memory ensembles across time

皮质记忆群随时间的重组

基本信息

批准号：
10680332
负责人：
Zachary E Zeidler
金额：
$ 7.18万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10680332
关键词：
Address Age Anatomy Anxiety Disorders Area Auditory Axon Behavior Behavior Control Behavioral Brain Brain Mapping Calcium Cells Coupling Cues Data Disease Event Foundations Freezing Fright Functional disorder Future Gene Expression Goals Head Image Immediate-Early Genes Label Light Link Maps Medial Mediating Memory Mentors Methods Microscope Modeling National Institute of Mental Health Nature Neurons Output Pattern Pilot Projects Population Post-Traumatic Stress Disorders Prefrontal Cortex Process Publishing Research Resistance Retrieval Role Testing Time Tissues Trauma Viral Physiology Work association cortex career cell type conditioned fear design effective intervention emotional experience experience experimental study fear memory genetic approach improved insight long term memory memory recall memory retrieval neural neural circuit novel optogenetics prevent recruit symposium therapeutic target timeline virus genetics

项目摘要

Project Summary Memory of a single event can last a lifetime. Certain experiences can guide behavior minutes, months, and years after the event has transpired. For this to happen, the brain must encode the relevant information from the event, retain it for an indeterminate amount of time, then retrieve that memory when given appropriate cues. Previous work has shown that retrieval of a fearful experience is behaviorally similar across recent and remote retrieval times of a memory, yet the neural circuits mediating that memory are importantly different across the memory timeline. In short, behavior remains stable while neural activity is dynamic. Evidence suggests that memories are reorganized across time – increasingly involve a distributed cortical network. Although we have identified several independent cortical regions that participate in remote memory, our understanding of how they interact at the and the nature of these changes is lacking My preliminary data indicates that an uninvestigated medial prefrontal cortex (mPFC) projection coordinates remote but not recent memory via projections to association cortex. Further exploration is needed to determine the specific activity patterns in these circuits during memory retrieval over time. These discoveries would reveal fundamental principles by which the brain organizes and retrieves salient experiences across time. The overall goal of this proposal is to investigate the cell-type specific changes that occur in mPFC ensembles as fear memories reorganize from recent to remote and to determine the nature of this reorganization. Based on published work from my mentor and my preliminary findings, my project will focus on the connection between mPFC and auditory association areas. To address these questions, I will use circuit-specific, optogenetic approaches to establish necessity and sufficiency of a mPFC–cortical association circuit for remote memory. This will address the functional role of these mPFC projection neurons. I will then use freely-moving calcium imaging to record the activity of these cells at both recent and remote memory timepoints in order to examine how these mPFC neurons encode and behavior and task variables across memory timepoints. Finally, with a combined viral-genetic approach, I will label activity-dependent ensembles while employing whole-brain circuit mapping to understand the anatomical relationship between recent and remote ensembles and their downstream connections. Together, these aims will reveal novel insights into the time-dependent changes in memory organization and enhance our understanding of mPFC function in organizing cortical networks, potentially identifying improved circuits to target for treatment of fear disorders (e.g. Post Traumatic Stress Disorder).

项目总结