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Functional interactions of the entorhinal cortex during systems consolidation

系统整合过程中内嗅皮层的功能相互作用

基本信息

批准号：
10389047
负责人：
Andrew Toader
金额：
$ 5.18万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
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：
2022-02-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10389047
关键词：
Alzheimer&apos s Disease Animal Model Animals Anterior Behavioral Behavioral Paradigm Brain Brain region Calcium Cells Chronic Clinical Clinical Treatment Communication Complex Dementia Disease Dissection Doctor of Philosophy Fellowship Fiber Functional disorder Goals Head Health Hippocampus (Brain)Human Image Imaging Device Impairment Implant Investigation Lead Learning Life Localized Lesion Major Depressive Disorder Memory Mental disorders Methods Modeling Monitor Mus Nature Neocortex Neurons Neurosciences Research Patients Photometry Physicians Play Post-Traumatic Stress Disorders Process Psychological reinforcement Public Health Research Retrieval Role Scientist Series Stimulus Symptoms Synapses System Techniques Technology Testing Time Time Study Training Universities Work base behavior measurement career cingulate cortex cognitive function design disabling symptom entorhinal cortex insight long term memory medical schools memory acquisition memory consolidation memory encoding memory recall memory retrieval neocortical neural correlate neuropsychiatric disorder novel optical fiber optogenetics programs recruit relating to nervous system response serial imaging skills theories two-photon virtual environment virtual reality

项目摘要

PROJECT SUMMARY Dysfunction in the stability of long-term memories is a core symptom of many neuropsychiatric disorders, including Alzheimer’s disease, major depression, and post-traumatic stress disorder. The process by which newly formed memories are stabilized into more permanent storage is known as memory consolidation. The hippocampus (HPC) has a well-established role in the initial formation and storage of memory. Over the course of days-to-months, memory recall is thought to become increasingly dependent on cortical regions, such as the anterior cingulate cortex (ACC). How memory is reorganized at the systems level between HPC and ACC remains poorly understood. Recent studies implicate an intermediate brain region, the entorhinal cortex (EC), as facilitating consolidation of memories. Disrupting the EC impairs the ability of new memories to be stored over long durations. However, it remains unclear when and how EC may contribute to memory consolidation. We hypothesize that EC is recruited at the time of learning to stabilize neurons and neural ensembles in ACC that represent a learned association. This project will test this by utilizing methods of monitoring and manipulating the dynamics of brain-wide circuits over extended periods of time through three specific aims. In aim one, we will first develop a novel virtual-reality based contextual learning task in head-fixed mice, allowing us to probe the learning and recall of memories throughout the duration of consolidation (weeks-to-months). The EC-ACC projection will be selectively inhibited at various time points to quantify its role in remote memory recall. In aim 2, we will record bulk neural activity from HPC, EC, and ACC using chronically implanted optical fibers (fiber photometry) to track interregional interactions and the emergence of neural correlates of memory during memory consolidation. In aim 3, we will perform two photon calcium imaging in ACC throughout memory retrieval including recent and remote time points. The EC-ACC projection will be selectively inhibited and the effect of this circuit on neural representations of memory at remote time points will be quantified. This investigation will fill a substantial gap in our understanding of systems consolidation and facilitate new insights into the distributed dynamics of memory in psychiatric health and disease. The applicant’s career goal is to be an academic physician-scientist with a research program aimed at bridging the gap between basic systems neuroscience research and clinical treatments. He is pursuing MD-PhD training at Weill Cornell Medical College and The Rockefeller University, and will develop research, scientific communication, and clinical expertise skills during this fellowship.

项目总结