Astrocytic Contributions to Long Term Memory & Synaptic Plasticity

星形胶质细胞对长期记忆的贡献

基本信息

批准号：
8402406
负责人：
Sarah Stern
金额：
$ 3.3万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-11-16 至 2014-11-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8402406
关键词：
AIDS Dementia Complex Adrenergic Agents Adrenergic Antagonists Affect Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Arousal Astrocytes Behavioral Binding Proteins Brain Brain Diseases Cell Culture Techniques Cells Complement Coupling D-arabitol Data Dendrites Development Disease Engineering Frequencies Glial Fibrillary Acidic Protein Glycogen Glycogen Phosphorylase Hippocampus (Brain)Hormones Injection of therapeutic agent Intermediate Filament Proteins Laboratories Lactate Transporter Learning Literature Long-Term Potentiation Maintenance Measures Mediating Memory Memory impairment Metabolic Molecular Target Neurodegenerative Disorders Neuroglia Neurons Norepinephrine Pathway interactions Peptide Elongation Factor 1 Phase Play Preparation Process Propranolol Protein Biosynthesis Proteins Rattus Reporting Research Design Resistance Role Small Interfering RNA Specificity Synapses Synaptic plasticity Testing Therapeutic Intervention Time Training Western Blotting Work adrenergic analog base behavior test beta-adrenergic receptor cognitive function conditioned fear emotional experience experience expression vector glycogenolysis in vivo inhibitor/antagonist knock-down locus ceruleus structure long term memory noradrenergic tool

AIDS Dementia Complex Adrenergic Agents Adrenergic Antagonists Affect Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Arousal Astrocytes Behavioral Binding Proteins Brain Brain Diseases Cell Culture Techniques Cells Complement Coupling D-arabitol Data Dendrites Development Disease Engineering Frequencies Glial Fibrillary Acidic Protein Glycogen Glycogen Phosphorylase Hippocampus (Brain)Hormones Injection of therapeutic agent Intermediate Filament Proteins Laboratories Lactate Transporter Learning Literature Long-Term Potentiation Maintenance Measures Mediating Memory Memory impairment Metabolic Molecular Target Neurodegenerative Disorders Neuroglia Neurons Norepinephrine Pathway interactions Peptide Elongation Factor 1 Phase Play Preparation Process Propranolol Protein Biosynthesis Proteins Rattus Reporting Research Design Resistance Role Small Interfering RNA Specificity Synapses Synaptic plasticity Testing Therapeutic Intervention Time Training Western Blotting Work adrenergic analog base behavior test beta-adrenergic receptor cognitive function conditioned fear emotional experience experience expression vector glycogenolysis in vivo inhibitor/antagonist knock-down locus ceruleus structure long term memory noradrenergic tool

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项目摘要

DESCRIPTION (provided by applicant): Memory consolidation is the process by which the newly learned information, which exists in a labile state, becomes a long-lasting memory that is resistant to disruption. Long-term memory consolidation requires de novo protein synthesis, and it is very likely that dendritic protein synthesis is also involved in this process. Long-term potentiation (LTP) is a persistent increase in synaptic strength, and is considered a cellular correlate for long-term memory. Like memory consolidation, late forms of LTP (L-LTP) also require protein synthesis, and have been shown to specifically require dendritic protein synthesis as well as somatic protein synthesis. Memories of emotional experiences such as those produced in the fear conditioning-based inhibitory avoidance (IA) paradigm, are subject to modulation by various hormones. Noradrenaline is released from the locus coeruleus during arousal and enhances memory via beta-adrenergic receptors. The same is true in regards to LTP, which is likewise modulated by noradrenaline. Recent evidence from our laboratory and others suggest that astrocytes play a larger role in both learning and memory and LTP than previously thought. By contributing lactate to neurons through glycogenolysis and transfer via monocarboxylate transporters, astrocytes are critical to memory consolidation and LTP maintenance (see preliminary data). Interestingly, beta-adrenergic receptors are present on astrocytes and have also metabolic effects in astrocytes when stimulated. This project will test the contribution of astrocytes to long-term memory and LTP. Specifically, it will test the hypothesis that astrocytes critically contribute to memory formation by providing astrocytic-neuronal coupling through lactate that supports the high-energy demands associated with activation of dendritic protein synthesis. Furthermore, it will test the hypothesis that the noradrenergic-dependent modulation of memory is mediated by the astrocytic-neuronal coupling.

描述（由申请人提供）：内存合并是在不稳定状态下的新学习信息成为一种持久的内存，该过程对破坏性有抵抗力。长期记忆巩固需要从头蛋白质的合成，并且很可能树突状蛋白合成也参与了这一过程。长期增强（LTP）是突触强度的持续增加，被认为是长期记忆的细胞相关性。像记忆巩固一样，LTP（L-LTP）的后期形式也需要蛋白质合成，并且已被证明需要树突状蛋白质合成以及体细胞蛋白质合成。情感经历的记忆，例如基于恐惧条件的抑制性避免（IA）范式在各种激素中受到调节的记忆。在唤醒期间，去甲肾上腺素是从核基因座释放的，并通过β-肾上腺素能受体增强记忆。关于LTP也是如此，这同样由去甲肾上腺素调节。我们实验室和其他实验室的最新证据表明，星形胶质细胞在学习和记忆和LTP中起着比以前想象的更大的作用。通过通过糖原分解并通过单羧酸盐转运蛋白转移神经元的乳酸，星形胶质细胞对于记忆巩固和LTP维持至关重要（请参阅初步数据）。有趣的是，β-肾上腺素能受体存在于星形胶质细胞上，并且在刺激时在星形胶质细胞中也具有代谢作用。该项目将测试星形胶质细胞对长期记忆和LTP的贡献。具体而言，它将检验以下假设：星形胶质细胞通过乳酸通过乳酸提供星形胶质细胞 - 神经元偶联来促进记忆形成，从而支持与树突状蛋白质合成相关的高能量需求。此外，它将检验以下假设：在星形细胞 - 神经元偶联中介导去甲肾上腺素能的记忆调节。