CELLULAR ANALYSIS OF SYNAPTIC CHANGES IN LEARNING

学习中突触变化的细胞分析

• 批准号: 6151606
• 负责人: MARC KLEIN
• 金额: $ 5.65万
• 依托单位: CLINICAL RESEARCH INSTITUTE OF MONTREAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151606
• 关键词: Aplysia; action potentials; behavioral /social science research tag; calcium flux; learning; neural plasticity; neurotransmitter transport; neurotransmitters; second messengers; synapses; tissue /cell culture

The goal of this project is to understand the physiological and biochemical processes that contribute to learning. Habituation, dishabituation and sensitization are widespread forms of learning that are caused by changes in transmission in the neural pathways that mediate behavior. Using the relatively simple nervous system of the marine mollusk Aplysia, several types of short and long-term synaptic plasticity have bene found to contribute to these forms of learning. The aim of this proposal is to extend the understanding of these cellular processes at individual synapses and to examine the contribution of some of the elements of the neural pathways to the alterations in overall output. Individual synapses will be studied in intact ganglia and in a reconstituted culture system of pairs of synaptically connected neurons that display virtually all of the forms of synaptic plasticity seen in situ. The contributions of pathway elements will be studied in intact ganglia. The specific aims of the project include: 1) Roles of second messengers in plasticity. This part of the project will examine the role of second-messenger systems in heterosynaptic facilitation, the increase in transmitter release that accompanies sensitization and dishabituation. a) Intracellular recording, voltage clamp and optical measurements of intracellular calcium concentration will be used in order to delineate the contributions of protein kinases A and C and CaM kinase to facilitation. b) Other experiments will test the hypothesis that some second messengers modulate release by acting at steps in the release process that are dependent on calcium influx while others act further downstream. 2) Changes in the pool of active synapses in plasticity. The hypothesis will be tested that a portion of the changes in transmission with plasticity is caused by the progressive silencing of individual synapses during synaptic depression and the recruitment of silent synapses in synaptic facilitation. These experiments will involve statistical analysis of synaptic transmission and direct observations of silent synapses which are recruited by facilitating stimuli. 3) Changes in action potential firing at different sites in the pathway as expressions of plasticity. The question to be examined here is how the changes in synaptic transmission are translated into changes in firing behavior.

该项目的目的是了解生理和 有助于学习的生化过程。习惯， 污染和敏化是广泛的学习形式， 是由神经途径传播变化引起的 中介行为。使用相对简单的神经系统 海洋软体动物Aplysia，几种类型的短期和长期突触 可塑性有益发现有助于这些形式的学习形式。这 该建议的目的是扩展对这些细胞的理解 单个突触的过程并检查某些的贡献 神经途径的元素的整体改变 输出。个人突触将在完整的神经节和 重构的培养系统成对的突触连接神经元 几乎显示在 原位。途径元素的贡献将完整研究 神经节。该项目的具体目的包括： 1）第二使者在可塑性中的作用。该项目的这一部分 将检查第二门徒系统在异突触中的作用 促进，随附的发射机释放的增加 敏化和污染。 a）细胞内记录，电压夹和光学测量值 细胞内钙浓度将用于描绘 蛋白激酶A和C和CAM激酶对 便利。 b）其他实验将检验以下假设。 Messenger通过在发行过程中的步骤进行操作来调节释放 取决于钙涌入，而其他人采取进一步行动 下游。 2）可塑性中主动突触的变化。假设 将测试与传输变化的一部分 可塑性是由单个突触的进行性沉默引起的 在突触抑郁症和募集无声突触的过程中 突触促进。这些实验将涉及统计 突触传播和直接观察的分析 通过促进刺激招募的突触。 3）动作电势射击的变化在路径的不同地点 作为可塑性的表达。这里要检查的问题是如何 突触传输的变化被转化为变化 射击行为。