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Defining Astrocyte Engram Ensembles During Memory Formation

定义记忆形成过程中的星形胶质细胞印迹整体

基本信息

批准号：
10722056
负责人：
Benjamin Deneen
金额：
$ 44万
依托单位：
BAYLOR COLLEGE OF MEDICINE
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：
2023-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722056
关键词：
3-Dimensional Ablation Acute Alzheimer&apos s Disease Amnesia Anxiety Astrocytes Behavior Behavioral Brain Calcium Cell Separation Cells Clozapine Cognition Data Dementia Diphtheria Toxin Disease Event Exhibits Experimental Designs Exposure to FOS gene Freezing Gene Expression Goals Hippocampus Image Immediate-Early Genes Impairment Label Learning Ligands Maps Measures Memory Memory impairment Molecular Molecular Analysis Morphology Mus Nature Neurons Output Oxides Physiological Play Population Post-Traumatic Stress Disorders Process Property Resolution Retrieval Role Signal Transduction Slice Specificity Synapses Synaptic plasticity System Testing Trauma Viral Virus calcium indicator conditioned fear dentate gyrus experimental study inducible gene expression insight memory encoding memory process memory recall memory retrieval nervous system disorder neuronal circuitry prospective reconstruction tool transcriptome sequencing two-photon

项目摘要

Summary Astrocytes play diverse and indispensable roles in brain function. Participating as a component of the ‘tripartite synapse’, a single astrocyte is estimated to contact up to 100,000 neuronal synapses in the hippocampus. Notably, studies have identified essential functions of astrocytes in hippocampal circuits, where astrocytes are required for regulating synaptic plasticity including LTP, a key process associated with learning and memory. Recent studies have shown that enhancing Gq-signaling in astrocytes promotes LTP and enhances acute memory, while impairing astrocyte function suppresses LTP and memory, highlighting central roles for astrocytes in memory-dependent tasks. Learning events invoke activity and plasticity among a discrete ensemble of cells. Activation of these ensembles by learning and reactivated during memory recall constitute the physical substrate of memory and are referred to as engrams. Despite the critical involvement of astrocytes in learning and memory processes, the study of memory engrams has been limited exclusively to neuronal ensembles. The goal of this proposal is to study the potential of astrocyte engrams as a substrate of memory and to understand the nature and function of hippocampal astrocyte ensembles. We have created a host of mouse lines and associated AAV-viral tools the enable us to label and manipulate astrocytes during learning events in the hippocampus. Preliminary studies with these tools indicate that we can label ensembles of astrocytes after learning and that reactivation of these same astrocytes promotes memory recall. Based on the strength of these preliminary data and the associated tools we have built, we propose the following specific aims. In specific aim1, we will label astrocyte ensembles after learning and characterize whether they exhibit engram properties. In specific aim2, we will manipulate the prospective engram astrocyte populations and determine whether they encode memory storage and recall. In specific aim3, we will characterize the cellular and molecular properties of these labeled astrocyte engram populations.

总结