NEUROTROPHIN MODULATION OF SYNAPTIC TRANSMISSION

神经营养因子对突触传递的调节

• 批准号: 2242549
• 负责人: Nina Tang Sherwood
• 金额: $ 1.3万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-13 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2242549
• 关键词: NEUROTROPHIN; MODULATION; SYNAPTIC; TRANSMISSION

The overall goal of this research proposal is to understand the short- term modulation of synaptic transmission by neurotrophins. There is increasing evidence that neurotrophin expression and neuronal excitability are intimately related. Neurotrophins are thus emerging, beyond traditional "growth and survival factors", as potential mediators of synaptic plasticity. Given the fundamental importance of rapid synaptic changes in nervous system functioning, a role for neurotrophins in the rapid mediation of synaptic plasticity is compelling. Furthermore, the likely involvement of these growth factors in such diseases as Alzheimer's and Parkinson's underscores the importance of understanding neurotrophin effects in the nervous system. Three questions will be investigated to understand the specific, short-term effects of neurotrophins on synaptic transmission: 1) How is synaptic transmission in neurons modulated by each member of the neurotrophin family? 2) At what locus, presynaptic or postsynaptic, do neurotrophins act to modulate synaptic transmission? 3) What are the specific molecular mechanisms by which neurotrophins modulate transmission? The proposed experiments will be addressed in CA1 hippocampal pyramidal neurons, which express the neurotrophins and their receptors in abundance, and are well-studied as a model of neuronal plasticity. Whole-cell patch clamp methods will be used to characterize synaptic currents in dissociated, "autaptic" neurons -- isolated neurons which have formed synapses on themselves. The use of such a simplified, yet functionally relevant model of a synapse will enable the understanding of specific neurotrophin effects on synaptic transmission, and help to elucidate the general role of neurotrophins in neuronal plasticity.

本研究的总体目标是了解短- 神经营养素对突触传递的调节作用。 有 越来越多的证据表明，神经营养因子的表达和神经元 兴奋性是密切相关的。 神经营养因子因此出现， 超越传统的“增长和生存因素”，作为潜在的调解人 突触可塑性。 鉴于快速的重要性， 神经系统功能的突触变化，神经营养因子的作用 在突触可塑性的快速调节中的作用是引人注目的。 此外，这些生长因子可能参与这种 阿尔茨海默氏症和帕金森氏症等疾病强调了 了解神经营养素在神经系统中的作用。 三 问题将被调查，以了解具体的，短期的 神经营养因子对突触传递的影响：1）突触如何 由神经营养因子的每个成员调制的神经元中的传递 家人？ 2)神经营养因子在突触前或突触后的哪个部位 来调节突触传递 3)有哪些具体 神经营养因子调节传递的分子机制？ 的 建议的实验将在CA 1海马锥体细胞中进行 神经元，表达神经营养素及其受体， 丰富，并作为神经元可塑性的模型进行了充分的研究。 全细胞膜片钳方法将用于表征突触 电流在分离的，“autaptic”神经元-孤立的神经元， 已经在自己身上形成了突触。 使用这种简化的，但 突触的功能相关模型将使我们能够理解 神经营养因子对突触传递的影响，并有助于 阐明神经营养因子在神经元可塑性中的一般作用。