Cellular and Molecular Basis of Long-Term Habituation

长期习惯的细胞和分子基础

• 批准号: 6673494
• 负责人: DAVID L GLANZMAN
• 金额: $ 30.87万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-12 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6673494
• 关键词: AMPA receptors; Aplysia; alternatives to animals in research; behavior test; behavioral /social science research tag; behavioral genetics; behavioral habituation /sensitization; biochemistry; biological models; electrophysiology; genetic transcription; gills; memory; neural plasticity; neurobiology; neuropharmacology; neuropsychology; sensorimotor system; stimulus /response; synapses; tissue /cell culture

DESCRIPTION (provided by applicant): Habituation is a basic, ubiquitous form of learning and memory. Nonetheless, the neurobiological basis of habituation in mammals, including man, is poorly understood. This situation is largely due to the vast complexity of the mammalian central nervous system. The long-term goal of this project is to use a simple, model organism, the marine snail Aplysia californica, to elucidate the cellular and molecular basis of habituation, particularly long-term habituation (LTH). When tactile stimuli are applied to the body surface of Aplysia, the animal exhibits with a defensive withdrawal reflex. In response to repeated tactile stimulation the reflex habituates. The withdrawal reflex exhibits both short- and long-term habituation. A major advantage of the withdrawal reflex for a study of habituation is that the neural circuitry that underlies the withdrawal reflex is well characterized. The proposed research will use a reduced preparation of Aplysia that can facilitate relating synaptic changes to behavioral changes. The synapse between the sensory and motor neurons that mediate the withdrawal reflex exhibits a form of long-term depression (LTD); this LTD may play a role in LTH in Aplysia. The potential role of LTD in LTH will be tested with electrophysiological and pharmacological experiments. In other experiments the cellular and molecular mechanisms of LTD will be characterized. One intriguing possibility is that LTD involves down-regulation of the function of a class of postsynaptic glutamate receptors (AMPA receptors). Functional down-regulation of AMPA receptors, perhaps due to changes in protein or mRNA synthesis, may also play a role in LTH. Pharmacological and, ultimately, molecular techniques will be used to test this idea. It is expected that the findings from the proposed research will contribute to a fundamental understanding of the processes that underlie learning and memory. Such an understanding will facilitate the development of treatments of diseases of memory, such as Alzheimer's.

描述（由申请人提供）：习惯是一种基本的、普遍存在的学习和记忆形式。尽管如此，人们对包括人类在内的哺乳动物习惯化的神经生物学基础知之甚少。这种情况很大程度上是由于哺乳动物中枢神经系统的巨大复杂性造成的。该项目的长期目标是使用一种简单的模式生物——海兔（Aplysia californica）来阐明习惯化的细胞和分子基础，特别是长期习惯化（LTH）。当触觉刺激施加到海兔的体表时，动物会表现出防御性退缩反射。为了响应重复的触觉刺激，反射会形成习惯。戒断反射表现出短期和长期的习惯。撤退反射对于习惯化研究的一个主要优点是撤退反射背后的神经回路得到了很好的表征。拟议的研究将使用减少的海兔制剂，以促进将突触变化与行为变化联系起来。介导撤退反射的感觉神经元和运动神经元之间的突触表现出一种长期抑郁（LTD）的形式；该LTD可能在海兔的LTH中发挥作用。 LTD 在 LTH 中的潜在作用将通过电生理学和药理学实验进行测试。在其他实验中，LTD 的细胞和分子机制将得到表征。一个有趣的可能性是，LTD 涉及一类突触后谷氨酸受体（AMPA 受体）功能的下调。 AMPA 受体的功能性下调（可能是由于蛋白质或 mRNA 合成的变化）也可能在 LTH 中发挥作用。药理学和最终的分子技术将被用来测试这个想法。预计拟议研究的结果将有助于对学习和记忆过程的基本理解。这种理解将有助于开发治疗记忆疾病（例如阿尔茨海默病）的方法。