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Aplysia Californica中学习和记忆的神经元机制。 该无脊椎动物的防御性戒断系统构成了为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。 此外，反射的基础的神经元电路相对众所周知。 该电路的一个中心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。 该动物的感觉运动突触强度的变化已显示与学习平行。 因此，感觉运动突触是垂直学习细胞分析的有利起点。 该项目将重点关注一种突触可塑性的形式，神经科学家长期以来一直认为，介导脊椎动物脑脑增强的学习和记忆。 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Hebbian增强作用与记忆联系起来。最近，已经表明，Aplysia的感觉运动突触表现出Hebbian增强性。 这一事实允许使用Aplysia以简单形式的戒断反射的简单形式的相关学习 - 经典条件形式来简化Hebbian增强作用。 该项目的目的是：（1）试图通过使用N-甲基-D-天冬氨酸受体的药理学拮抗剂（已知介导HEBBIAN可塑性的受体类型）来提供证据表明Hebbian可塑性在经典调节中起作用； （2）确定经典条件是否涉及Hebbian可塑性和突触竞争之间的相互作用； （3）确定经典条件是否涉及Hebbian可塑性与单胺能发射器激活的细胞途径之间的相互作用； （4）试图发现维持Hebbian增强的长期细胞变化。预计拟议的研究的发现将有助于理解强调学习和记忆的过程。 这样的理解将是改善记忆疾病的疗法的基础，例如阿尔茨海默氏症。