HEBBIAN LONG-TERM POTENTIATION AND LEARNING

描述(摘自申请者摘要)：长期目标 这个项目是为了阐明学习和记忆的神经机制。 在海洋软体动物中。防御性撤退反射 构成了这一目的的一个重要的模式系统。这个 反射表现出几种学习形式，包括经典的条件反射。 此外，作为戒断反射基础的神经元回路， 尤其是它的单突触成分--感觉和神经之间的突触 运动神经元--相对简单，也很容易理解。神经元改变 在感觉运动突触已经被证明是平行的，并可能 在戒断反射的行为调整中的机械性作用。 因此，这种突触是神经生物学研究的有用起点。 海兔的学习分析。中环的另一个优势 海兔的感觉运动性突触是可以在细胞内重组的 文化。这些体外突触极大地促进了实验分析 与学习相关的细胞修饰。 拟议中的实验将集中在一种已知的突触可塑性上。 作为Hebbian长时程增强(LTP)，神经元变化的一种形式 与脊椎动物的记忆和认知密切相关。Hebbian LTP有 最近描述了海兔感觉运动型突触在细胞培养中的作用。 这项建议的具体目的是分析细胞机制 这种无脊椎动物LTP的新形式，并确定它在 在海岛学习。计划中的实验将利用细胞内的突触 培养，以及组成中枢神经系统的制剂 海兔属。将通过实验解决的一些问题包括： (I)在海兔感觉运动性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，调节了 海兔感觉运动性突触的LTP？(Iii)Hebbian增强 海兔感觉运动性突触在经典条件反射中的作用 海兔的戒断反射？这些问题将通过以下方式解决 电生理和成像技术，其中包括：Quantal 分析；视频荧光显微检测结构变化和 海兔活体神经元细胞内钙离子的变化及实验 涉及到戒断的经典条件反射的细胞模拟 条件反射。 拟议的研究将作为改进我们的 对人类学习和记忆的理解。因此，它可能有助于 改善人类记忆相关的疾病，如阿尔茨海默氏症。

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.