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.

概括星形胶质细胞在大脑功能中起潜水员和必不可少的作用。作为三方的组成部分突触'，估计单个星形胶质细胞在海马中接触多达100,000个神经元突触。尤其，研究已经确定了在海马电路中星形胶质细胞的重要功能，其中星形胶质细胞需要调节包括LTP在内的突触可塑性，这是与学习和记忆有关的关键过程。最近的研究已经表明，增强星形胶质细胞中的GQ信号会促进LTP并增强急性记忆力，同时损害星形胶质细胞功能抑制了LTP和内存，突出了星形胶质细胞中的主要角色任务。学习事件在分散的细胞集合中调用活性和可塑性。这些激活通过学习和重新激活记忆期间的合奏构成记忆的物理基质，是称为实体。尽管星形胶质细胞在学习和记忆过程中至关重要，但该研究内存象征仅限于神经元合奏。该提议的目的是研究星形胶质细胞ENGRAM作为记忆的基板的潜力，并了解海马的性质和功能星形胶质细胞合奏。我们创建了许多鼠标线和关联的AAV病毒工具，使我们能够标记和在海马学习事件中操纵星形胶质细胞。使用这些工具的初步研究表明我们可以在学习后标记星形胶质细胞的组合，并且这些相同星形胶质细胞的重新激活会促进记忆回忆。根据这些初步数据的强度和我们构建的相关工具，我们建议以下特定目标。在特定的AIM1中，我们将在学习和表征之后标记星形胶质细胞合奏它们是否暴露了Engram属性。在特定的AIM2中，我们将操纵前瞻性ENGRAM Astrocyte 种群并确定它们是否编码内存存储和回忆。在特定的AIM3中，我们将描述这些标记的星形胶质细胞器官种群的细胞和分子特性。