HEBBIAN LONG-TERM POTENTIATION AND LEARNING IN APLYSIA

海兔的赫比长时程增强和学习

• 批准号: 2864099
• 负责人: DAVID L GLANZMAN
• 金额: $ 27.49万
• 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 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2864099
• 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.

本研究的长期目标是阐明一种简单生物- 这种无脊椎动物的防御性撤退系统构成了一个重要的模型系统，用于这一目的。 反射表现出几种简单的学习形式，包括经典条件反射。 此外，作为反射基础的神经元回路也相对较好地被理解。 这个回路的一个中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。 这种动物的感觉运动突触强度的变化已经被证明与学习平行。 因此，感觉运动突触是一个有利的起点，细胞分析的学习，在失智症。 该项目将集中在突触可塑性的一种形式，长期以来一直被神经科学家认为是介导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，以及脊椎动物表现出的学习形式的复杂性，已经证明很难令人信服地将赫布增强和记忆联系起来。最近，它已被证明，感觉运动突触的Aesthesia表现出赫布增强。 这一事实允许使用Aesthesia的一个简单的形式的联想学习的经典条件反射的撤退赫布增强的作用的还原分析。 该项目的目标是：（1）通过使用N-甲基-D-天冬氨酸受体（已知介导Hebbian可塑性的受体类型）的药理学拮抗剂，试图提供Hebbian可塑性在经典条件反射中发挥作用的证据;（2）确定经典条件反射是否涉及Hebbian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和单胺能递质激活的细胞通路之间的相互作用;（4）试图发现维持赫布增强的长期细胞变化。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。 这样的理解将作为治疗的基础，以改善记忆疾病，如阿尔茨海默氏症。