Cellular and Molecular Basis of Long-Term Habituation

长期习惯的细胞和分子基础

• 批准号: 6903364
• 负责人: DAVID L GLANZMAN
• 金额: $ 5.08万
• 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 2004-08-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6903364
• 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（申请人提供）：习惯是一种基本的，无处不在的学习和记忆形式。但是，包括人在内的哺乳动物中习惯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严重复杂性。该项目的长期目标是使用一种简单的模型生物体，即船用蜗牛Aplysia加州，以阐明习惯的细胞和分子基础，尤其是长期习惯（LTH）。当将触觉刺激应用于垂体的身体表面时，动物表现出防御性戒断反射。为了反复触觉刺激，反射习惯。戒断反射表现出短期和长期习惯。戒断反射的主要优势是研究戒断反射的神经回路的表征。拟议的研究将使用降低的Aplysia制备，这可以促进突触变化与行为变化相关联。介导戒断反射的感觉和运动神经元之间的突触表现出长期抑郁症的形式（LTD）；该有限公司可能在Aplysia的LTH中发挥作用。 LTD在LTH中的潜在作用将通过电生理和药理实验进行测试。在其他实验中，将表征LTD的细胞和分子机制。一种有趣的可能性是LTD涉及一类突触后谷氨酸受体（AMPA受体）的功能下调。 AMPA受体的功能下调可能是由于蛋白质或mRNA合成的变化所致，也可能在LTH中起作用。药理学，最终将使用分子技术来测试这一想法。预计拟议研究的发现将有助于对学习和记忆的过程的基本理解。这样的理解将促进诸如阿尔茨海默氏病等记忆疾病的治疗方法的发展。