HEBBIAN LONG-TERM POTENTIATION AND LEARNING

Hebbian 长期增强和学习

• 批准号: 2735606
• 负责人: DAVID L GLANZMAN
• 金额: $ 22.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-03 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2735606
• 关键词: Aplysia; NMDA receptors; behavioral /social science research tag; calcium flux; conditioning; electrophysiology; fluorescence microscopy; learning; long term potentiation; mixed tissue /cell culture; motor neurons; reflex; sensorimotor system; synapses; video microscopy

DESCRIPTION (Adapted from applicant's abstract): The long-term objective of this project is to elucidate the neuronal mechanisms of learning and memory in the marine mollusk Aplysia californica. The defensive withdrawal reflex of this animal constitutes an important model system for this purpose. The reflex exhibits several forms of learning, including classical conditioning. Moreover, the neuronal circuitry which underlies the withdrawal reflex, particularly its monosynaptic component--the synapse between sensory and motor neurons--is relatively simple and well-understood. Neuronal changes at the sensorimotor synapse have been shown to parallel, and may have mechanistic roles in, behavioral modification of the withdrawal reflex. Therefore, this synapse is a useful starting point for a neurobiological analysis of learning in Aplysia. An additional advantage of central sensorimotor synapses of Aplysia is that they can be reconstituted in cell culture. These in vitro synapses greatly facilitate experimental analysis of learning-related cellular modifications. The proposed experiments will focus on a form of synaptic plasticity known as Hebbian long-term potentiation (LTP), a form of neuronal change prominently implicated in vertebrate memory and cognition. Hebbian LTP has recently been described for Aplysia sensorimotor synapses in cell culture. The specific aims of this proposal are to analyze the cellular mechanisms of this novel form of invertebrate LTP, and to determine its potential role in learning in Aplysia. The proposed experiments will utilize synapses in cell culture, as well as preparations comprising the central nervous system of Aplysia. Some of the questions which will be experimentally addressed are: (i) Does transmission at Aplysia sensorimotor synapses involve N-methyl-D-aspartate (NMDA)-related receptors? Activation of NMDA receptors is known to mediate the induction of Hebbian LTP of vertebrate synapses. (ii) What are the long-term cellular changes that mediate the expression of LTP of Aplysia sensorimotor synapses? (iii) Does Hebbian potentiation of Aplysia sensorimotor synapses play a role in classical conditioning of the withdrawal reflex of Aplysia? These questions will be addressed utilizing both electrophysiological and imaging techniques, among which are: quantal analysis; video fluorescence microscopic detection of structural changes and changes in intracellular calcium, in living Aplysia neurons; and experiments involving a cellular analogue of classical conditioning of the withdrawal reflex. The proposed research will serve as the basis for improving our understanding of human learning and memory. It may thereby contribute to ameliorating human memory-associated diseases, such as Alzheimer's.

描述（改编自申请人摘要）：长期目标 本项目旨在阐明学习和记忆的神经机制 在海洋软体动物加州海蛞蝓中。 防御性退缩反射 这种动物的模型系统构成了这一目的的重要模型系统。 的 反射表现出几种学习形式，包括经典条件反射。 此外，神经回路的基础撤回反射， 特别是它的单突触成分--感觉和 运动神经元--相对简单且易于理解。 神经元变化 在感觉运动突触上的神经元被证明是平行的， 机械的作用，行为修改的撤退反射。 因此，这个突触是神经生物学的一个有用的起点 分析学习在亚洲。 中央的另一个优势 感觉运动突触的一个重要特点是它们可以在细胞内重建 文化 这些体外突触极大地方便了实验分析 与学习相关的细胞变化。 拟议的实验将集中在一种形式的突触可塑性， Hebbian长时程增强（LTP），一种神经元变化形式 与脊椎动物的记忆和认知有着重要的联系。 Hebbian LTP拥有 最近被描述为细胞培养中的感觉运动突触。 这项建议的具体目的是分析细胞机制， 这种新形式的无脊椎动物LTP，并确定其潜在的作用， 学习在亚洲 拟议的实验将利用细胞中的突触 培养物，以及包含中枢神经系统的制剂， 阿托西亚。 将通过实验解决的一些问题是： (i)感觉运动突触的传递是否涉及 N-甲基-D-天冬氨酸（NMDA）相关受体？ NMDA受体的激活 已知介导脊椎动物突触的Hebbian LTP的诱导。 (ii)什么是长期的细胞变化，介导的表达， 感觉运动突触的LTP？ (iii)Hebbian增强是否 感觉运动突触失活在神经元的经典条件反射中起作用 失忆的退缩反射？ 这些问题将利用 电生理和成像技术，其中包括：量子 分析;视频荧光显微镜检测结构变化， 细胞内钙的变化，在活的神经元;和实验 涉及一种典型的戒断条件反射的细胞类似物 反射。 拟议的研究将作为改善我们的基础， 了解人类的学习和记忆。 因此，它可能有助于 改善人类记忆相关疾病，如阿尔茨海默氏症。