HEBBIAN LONG-TERM POTENTIATION AND LEARNING IN APLYSIA

该项目的长期目标是阐明一种简单生物——加利福尼亚海百合的学习和记忆的神经元机制。这种无脊椎动物的防御撤退系统构成了这一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，作为反射基础的神经回路也得到了相对较好的理解。这个回路的中心部分是调节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平行学习有关。因此，感觉运动突触是一个有利的起点，为细胞分析学习在澳大利亚。该项目将重点研究一种突触可塑性，神经科学家长期以来一直认为这种可塑性可以调节脊椎动物大脑的学习和记忆。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，证明很难令人信服地将Hebbian增强和记忆联系起来。最近，有研究表明，海马的感觉运动突触表现出Hebbian增强。这一事实允许使用应用程序对赫比强化在联想学习的简单形式-退缩反射的经典条件反射中的作用进行还原论分析。该项目的目标将是：(1)试图通过使用n -甲基- d -天冬氨酸受体（已知介导Hebbian可塑性的受体类型）的药理拮抗剂，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Hebbian可塑性与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Hebbian增强的长期细胞变化。预计这项研究的结果将有助于理解强调学习和记忆的过程。这样的认识将为改善阿尔茨海默氏症等记忆疾病的治疗提供基础。

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.