Growth Factors and Memory Formation

生长因子和记忆形成

基本信息

批准号：
8370005
负责人：
Thomas J Carew
金额：
$ 37.92万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8370005
关键词：
Accidents Address Adult Alzheimer&apos s Disease Aplysia Behavioral Binding Biological Models Brain Clinical Cognition Disorders Cognitive Data Development Developmental Process Disease Event Extracellular Protein Family Goals Growth Factor Health Individual Injury Knowledge Learning Link Maintenance Marines Mediating Memory Memory impairment Mental Health Mission Molecular Motor National Institute of Mental Health Neurodegenerative Disorders Neurons Neurosciences Outcome Phase Play Post-Traumatic Stress Disorders Preparation Publishing Research Project Grants Research Proposals Role Seminal Sensory Services Signal Transduction Stroke Synapses Synaptic plasticity System Testing Therapeutic Agents Time Training base effective therapy forging long term memory memory process molecular dynamics neuronal cell body neurotrophic factor novel novel strategies receptor research study spatiotemporal therapeutic target

项目摘要

DESCRIPTION (provided by applicant): One of the greatest challenges in modern neuroscience is to achieve an understanding of how the brain acquires, stores and retrieves information. A particularly exciting new development in exploring this general question is the recent identification of the possible role of growth factors, once considered to function mainly in brain development, in synaptic plasticity and memory in the adult. While this idea is truly seminal, a causal role of growth factors in memory formation has yet to be established. Thus the broad, long-term goal of this research project is to elucidate in mechanistic detail the ways in which growth factors participate in the formation and maintenance of long-term memories. To achieve this goal we will explore two interrelated Specific Aims. In AIM 1 we will test the hypothesis that growth factor signaling plays an essential role in memory formation and its underlying synaptic plasticity, and in Aim 2 we will test the hypothesis that growth factors re-employ molecular signaling cascades originally engaged in development in the service of adult memory formation and synaptic plasticity. Of direct relevance to the health-related mission of the NIMH, these two Aims will address a major challenge in mental health: to achieve a basic understanding of the brain mechanisms that are engaged in normal memory formation, and how those mechanisms are impaired when memory is compromised by disease or injury. Thus, understanding the molecular mechanisms whereby growth factors contribute to normal memory formation can provide an important and novel means of identifying therapeutic targets for a variety of health related cognitive disorders. To directly explore how growth factors participate i memory formation requires multiple levels of analysis (behavioral, cellular, synaptic, and molecular levels). Aplysia californica is a powerful model system to address this question because it allows such a simultaneous multi-level analysis, as well as a time-dependent analysis of when critical changes occur, and a spatial analysis of where changes occur in different regions of individual neurons. Thus a unique feature of this proposal is our use of a system that has the potential to demonstrate causal linkages between growth factor-mediated memory formation and the temporal and spatial features of the underlying synaptic mechanisms. PUBLIC HEALTH RELEVANCE: A major challenge in mental health is to achieve a basic understanding of the brain mechanisms that are engaged in normal memory formation, and how those mechanisms are impaired when memory is compromised by disease or injury, such as in Alzheimer's Disease, Post-Traumatic Stress Disorders, and in victims of accidents or strokes. Thus, the major focus of this project, understanding the molecular mechanisms whereby growth factors contribute to normal memory formation, can provide a means of developing effective therapies for a wide range of cognitive problems involving memory impairment.

描述（由申请人提供）：现代神经科学面临的最大挑战之一是了解大脑如何获取、存储和检索信息。在探索这个普遍问题时，一个特别令人兴奋的新进展是最近确定了生长因子的可能作用，曾经被认为主要在大脑发育，成人突触可塑性和记忆力。虽然这个想法确实具有开创性，但生长因子在记忆形成中的因果作用尚未确定。因此，该研究项目的广泛、长期目标是详细阐明生长因子参与长期记忆形成和维持的方式。为了实现这一目标，我们将探索两个相互关联的具体目标。在目标 1 中，我们将检验生长因子信号在记忆形成及其潜在突触可塑性中发挥重要作用的假设，在目标 2 中，我们将检验生长因子重新利用最初参与服务开发的分子信号级联的假设成人记忆形成和突触可塑性。这两个目标与 NIMH 的健康相关使命直接相关，将解决心理健康方面的重大挑战：基本了解参与正常记忆形成的大脑机制，以及这些机制在记忆过程中如何受到损害。因疾病或受伤而受到损害。因此，了解生长因子有助于正常记忆形成的分子机制可以为识别各种健康相关认知障碍的治疗靶点提供重要而新颖的方法。要直接探索生长因子如何参与记忆形成，需要进行多个级别的分析（行为、细胞、突触和分子水平）。海兔是解决这个问题的强大模型系统，因为它允许同时进行多级分析，以及对何时发生关键变化进行时间依赖性分析，以及对单个神经元不同区域发生变化的位置进行空间分析。因此，该提案的一个独特特征是我们使用了一个系统，该系统有可能证明生长因子介导的记忆形成与潜在突触机制的时间和空间特征之间的因果关系。公共卫生相关性：心理健康方面的一个主要挑战是对参与正常记忆形成的大脑机制有一个基本的了解，以及当记忆因疾病或损伤（例如阿尔茨海默氏病）而受损时，这些机制如何受损。 -创伤性应激障碍，以及事故或中风的受害者。因此，该项目的主要焦点是了解生长因子有助于正常记忆形成的分子机制，可以为开发针对涉及记忆障碍的广泛认知问题的有效疗法提供一种手段。