MECHANISMS OF MAMMALIAN NEURONAL INTEGRATION

哺乳动物神经元整合机制

• 批准号: 2265575
• 负责人: Robert E Fyffe
• 金额: $ 22.55万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265575
• 关键词: axon; cats; cell cell interaction; cell type; choline; chordate locomotion; computational neuroscience; electron microscopy; electrophysiology; gamma aminobutyrate; glycine; immunocytochemistry; interneurons; light microscopy; microelectrodes; motor neurons; nerve endings; neurophysiology; neurotransmitter receptor; receptor expression; serotonin; spinal cord; spinal nerves; synapses

The long term objective is to improve understanding of the synaptic and integrative mechanisms involved in motor control circuits in the mammalian spinal cord. These mechanisms play vital roles in all parts of the central nervous system and may, when unregulated or damaged, be involved in certain pathophysiological states such as spasticity, epilepsy, and neurodegenerative disorders. Synaptic location is a major factor in determining synaptic efficacy because, as a result of the passive cable (electrotonic) properties of dendrites, synaptic potentials generated by synapses at distal dendritic locations are severely attenuated and distorted as they propagate towards the cell body. But there may also exist mechanisms to compensate for this attenuation, including the possibility that there are more receptors present at distal synapses compared to synapses close to the soma. Understanding the structural and molecular basis of synaptic integration thus requires a precise knowledge of the distribution of different classes of synapses and their corresponding neurotransmitter receptors on individual identified neurons in vivo. Our working hypothesis is that the integrative properties of neurons and the efficacy of synaptic connections are intimately linked to neuron-specific patterns of receptor expression and synaptic input. To test this hypothesis the specific aims of this proposal are to answer the following questions: l) what are the precise patterns of receptor distribution in different cell types and are there differences in receptor cluster size and/or density in different compartments (e.g. proximal vs distal dendrites)? and 2) how are different classes of synaptic inputs organized over the surface of single neurons? These questions will be answered in two ways: l) by using immunocytochemistry combined with intracellular staining to determine receptor expression patterns in individual, physiologically identified, neurons in vivo and 2) by determining the precise distribution of immunohistochemically defined presynaptic terminals in contact with single intracellularly stained neurons in vivo. Each study will also use electronmicroscopy to examine the ultrastructural features of identified synapses. This study will focus on identified alpha- and gamma-motoneurons, Renshaw cells and Ia inhibitory interneurons. Among the transmitter/receptor families to be studied are those involved in glycinergic, GABA-ergic, glutamatergic, monoaminergic and cholinergic neurotransmission, all of which play important roles in segmental motor control. This highly integrative approach will produce results of general significance for advancing understanding of synaptic and integrative mechanisms as well as novel details on the segmental motor system.

长期目标是提高对突触和突触的理解 哺乳动物运动控制电路的整合机制 脊髓。这些机制在中央的各个部分都发挥着至关重要的作用。 神经系统，当不受调节或受损时，可能参与 某些病理生理状态，如痉挛、癫痫等 神经退行性疾病。突触位置是一个主要因素 确定突触功效，因为，由于无源电缆 树突的（电紧张）特性，由产生的突触电位 远端树突位置的突触严重减弱 当它们向细胞体传播时会发生扭曲。但也可能有 现有机制可以补偿这种衰减，包括 远端突触处可能存在更多受体 与靠近体细胞的突触相比。了解结构和 因此，突触整合的分子基础需要精确的知识 不同类别突触的分布及其 各个已识别神经元上相应的神经递质受体 体内。我们的工作假设是，综合属性 神经元和突触连接的功效密切相关 受体表达和突触输入的神经元特异性模式。到 检验这一假设 该提案的具体目标是回答 以下问题：l) 受体的精确模式是什么 不同细胞类型的分布及受体是否存在差异 不同区室中的簇大小和/或密度（例如近端与 远端树突）？ 2）不同类别的突触输入有何不同 组织在单个神经元的表面上？这些问题将会 有两种方式回答：l) 通过使用免疫细胞化学结合 细胞内染色以确定受体表达模式 个体、生理学鉴定的体内神经元和 2) 确定免疫组织化学定义的精确分布 突触前末梢与单细胞内染色接触 体内的神经元。每项研究还将使用电子显微镜来检查 已识别突触的超微结构特征。本研究将重点 已识别的 α 和 γ 运动神经元、Renshaw 细胞和 Ia 抑制性中间神经元。在发射机/受体家族中 研究涉及甘氨酸能、GABA 能、谷氨酸能、 单胺能和胆碱能神经传递，所有这些都起作用 在节段运动控制中发挥重要作用。这种高度集成的 方法将产生对推进具有普遍意义的成果 了解突触和整合机制以及新颖的 节段运动系统的详细信息。