HEBBIAN LONG-TERM POTENTIATION AND LEARNING IN APLYSIA

海兔的赫比长时程增强和学习

• 批准号: 6617978
• 负责人: DAVID L GLANZMAN
• 金额: $ 21.16万
• 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 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617978
• 关键词: Aplysia; NMDA receptors; association learning; behavioral /social science research tag; calcium flux; calmodulin; conditioning; electrical potential; electrophysiology; long term potentiation; mechanical pressure; memory; microelectrodes; mixed tissue /cell culture; motor neurons; neural plasticity; organ culture; perfusion; reflex; sensorimotor system; serotonin; synapses; voltage /patch clamp

The long-term objective of this project is to elucidate the neuronal mechanisms of learning and memory in a simple organism, Aplysia californica. The defensive withdrawal system of this invertebrate constitutes an important model system for this purpose. The reflex exhibits several simple forms of learning, including classical conditioning. Furthermore, the neuronal circuitry that underlies the reflex is relatively well understood. A central component of this circuitry is the synaptic connection between the sensory and motor neurons that mediate the reflex. Changes in the strength of the sensorimotor synapse have been shown to parallel learning by this animal. The sensorimotor synapse is therefore an advantageous starting point for a cellular analysis of learning in Aplysia. The project will focus on a form of synaptic plasticity that has long been thought by neuroscientists to mediate learning and memory in the vertebrate brain-Hebbian potentiation. Due to the brain's tremendous complexity, however, as well as to the sophistication of the forms of learning exhibited by vertebrates, it has proved difficult to convincingly link Hebbian potentiation and memory. Recently, it has been shown that sensorimotor synapses of Aplysia exhibit Hebbian potentiation. This fact permits the use of Aplysia for a reductionist analysis of the role of Hebbian potentiation in a simple form of associative learning-classical conditioning of the withdrawal reflex. The goal of the project will be: (1) to attempt to provide evidence that Hebbian plasticity plays a role in classical conditioning through the use of pharmacological antagonists of N-methyl-D-aspartate receptors, the receptor type known to mediate Hebbian plasticity; (2) to determine whether classical conditioning involves an interaction between Hebbian plasticity and synaptic competition; (3) to determine whether classical conditioning involves an interaction between Hebbian plasticity and cellular pathways activated by monoaminergic transmitters; and (4) to attempt to discover the long-term cellular changes that maintain Hebbian potentiation. It is expected that the findings from the proposed research will contribute to an understanding of the processes that underline learning and memory. Such an understanding will serve as a basis for treatments to ameliorate diseases of memory, such as Alzheimer's.

该项目的长期目标是阐明简单生物体（海兔）学习和记忆的神经元机制。 这种无脊椎动物的防御性撤退系统构成了用于此目的的重要模型系统。 反射表现出几种简单的学习形式，包括经典条件反射。 此外，反射背后的神经回路也相对容易理解。 该电路的核心组成部分是介导反射的感觉神经元和运动神经元之间的突触连接。 感觉运动突触强度的变化已被证明与这种动物的学习平行。 因此，感觉运动突触是海兔学习细胞分析的有利起点。 该项目将重点研究一种突触可塑性，神经科学家长期以来认为这种可塑性可以调节脊椎动物大脑的学习和记忆——赫布增强。 然而，由于大脑的巨大复杂性以及脊椎动物所表现出的学习形式的复杂性，事实证明很难令人信服地将赫布增强和记忆联系起来。最近，研究表明海兔的感觉运动突触表现出赫布增强作用。 这一事实允许使用海兔来对赫布增强作用的简化分析，这种作用是一种简单形式的联想学习——退缩反射的经典条件作用。 该项目的目标是：（1）尝试提供证据，证明赫布可塑性通过使用 N-甲基-D-天冬氨酸受体的药理学拮抗剂在经典条件反射中发挥作用，N-甲基-D-天冬氨酸受体是已知介导赫布可塑性的受体类型； （2）确定经典条件反射是否涉及赫布可塑性和突触竞争之间的相互作用； (3) 确定经典条件反射是否涉及赫布可塑性与单胺能递质激活的细胞通路之间的相互作用； (4) 尝试发现维持赫布增强作用的长期细胞变化。预计拟议研究的结果将有助于理解强调学习和记忆的过程。 这种理解将成为治疗改善记忆疾病（例如阿尔茨海默病）的基础。