VERTEBRATE NEURONAL INTERACTIONS AND ELECTROGENESIS

脊椎动物神经元相互作用和发电

• 批准号: 6033052
• 负责人: DONALD S FABER
• 金额: $ 1万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-11 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6033052
• 关键词: Mauthner's neuron; NMDA receptors; afferent nerve; alternatives to animals in research; brain stem; calcium; cell cell interaction; chlorine; dendrites; dopamine; gamma aminobutyrate; goldfish; guanine nucleotide binding protein; innervation; intracellular; long term potentiation; medulla oblongata; neural information processing; neural inhibition; neural plasticity; neural transmission; protein kinase A; spreading cortical depression; synapses; tetany

The long-term objective of the proposed research is to relate mechanistic information about the basic properties and activity-dependent plasticity of synaptic connections between identified neurons in the vertebrate central nervous system to the operation of the networks in which they are embedded. The experimental model used in these studies is the goldfish Mauthner (M-) cell and its medullary circuits. This neuron mediates an escape response triggered by sensory stimuli from the eighth nerve, and both the electrotonic and chemical synaptic responses triggered by the eighth nerve input exhibit activity-dependent modifications, namely, long- term potentiation (LTP) and depression (LTD). These synaptic responses are also enhanced by the endogenous modulator dopamine. Intradendritic recordings from the M-cell dendrite will be combined with recordings from single afferents and with nerve stimulation, to test specific hypotheses. about the mechanisms of these modifications. The first aim is to test the hypothesis that the enhancements of synaptic transmission produced by dopamine and LTP share common intracellular regulatory mechanisms, and that dopamine influences the effectiveness of various tetanizing paradigms. This proposal builds on evidence that dopamine acts through a cAMP-dependent pathway. The second aim is to determine the mechanism by which pairing inhibition with a weak tetanus induces LTD. The role of metabotropic glutamate receptors and intracellular Ca++ will be tested. In both aims, the site of the synaptic modification will be determined, with pharmacological methods and postsynaptic injections of compounds that directly interfere with or mimic the effects of the implicated intracellular regulatory pathways. In the third aim, pre- and postsynaptic intracellular recordings will be used to compare the LTP and LTD induced at single connections with modifications in the population responses, and to test the hypothesis that modifications of the strength of single connections depend on their initial efficacy. Particular attention will be paid to the role of silent connections in these phenomena. The fourth aim is concerned with short-term plasticity at these synapses and those between the M-axon and identified cells postsynaptic to it in the brainstem, connections which show a marked depression. Specific molecular probes will be injected presynaptically, to determine the molecular determinants of the probability of release and its plasticity. The data will be analyzed statistically, including the techniques of quantal analysis. The mechanisms of synaptic transmission that will be studied in the proposed research are relevant to numerous health-related issues, such as learning and memory and environmental adaptations of nervous system function. Silent synaptic connections potentially provide the substrate for nervous system adaptation, as a function of experience, during development and in response to traumatic injury or stroke.

拟议研究的长期目标是关联机械 有关基本特性和活动依赖性可塑性的信息 脊椎动物中已识别神经元之间的突触连接 中枢神经系统到网络的操作 嵌入。这些研究中使用的实验模型是金鱼 Mauthner（M-）细胞及其髓质电路。这个神经元介导 逃脱反应是由感官刺激从第八神经引起的， 电动和化学突触反应均由 第八神经输入表现出活性依赖性修饰，即长期 术语增强（LTP）和抑郁症（LTD）。这些突触反应是 内源性调节剂多巴胺也增强了。内端 M细胞树突的录音将与来自 单一传入和神经刺激，以检验特定的假设。 关于这些修饰的机制。第一个目的是测试 假设突触传播产生的增强 多巴胺和LTP具有共同的细胞内调节机制，并且 多巴胺会影响各种四人化的有效性 范式。该提议基于证据，表明多巴胺通过 依赖营的途径。第二个目的是通过 与破伤风弱的抑制作用诱导了有限公司。的作用 将测试代谢性谷氨酸受体和细胞内Ca ++。在 这两个目的，都将确定突触修饰的位点，并在 药理学方法和突触后注射化合物 直接干扰或模仿牵连的影响 细胞内调节途径。在第三个目标中，突触前后 细胞内记录将用于比较LTP和LTD诱导的 在人口响应中修改的单一连接处，以及 测试单个强度的修改的假设 连接取决于它们的初始功效。特别关注 在这些现象中付出了沉默联系的作用。第四目标 与这些突触和这些有关的短期可塑性有关 在M X轴和发现的细胞之间的突触后， 脑干，显示出明显抑郁症的连接。特异性分子 探针将在突触前注射，以确定分子 释放概率及其可塑性的决定因素。数据 将通过统计分析，包括数量的技术 分析。 突触传播的机制将在 拟议的研究与许多与健康有关的问题有关，例如 神经系统的学习和记忆和环境改编 功能。无声突触连接可能会提供基材 对于神经系统的适应，作为经验的函数， 开发并应对创伤或中风。