NEUROTROPHIN MODULATION OF SYNAPTIC TRANSMISSION

这项研究建议的总体目标是了解以下方面的不足- 神经营养因子对突触传递的时程调节。的确有 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。因此，神经营养因子正在出现， 超越传统的“成长和生存因素”，作为潜在的调解人 突触的可塑性。考虑到快速的基本重要性 神经营养因子在神经系统功能中的突触变化 在突触的快速调节中，可塑性是引人注目的。 此外，这些增长因素可能参与了 阿尔茨海默氏症和帕金森氏症等疾病强调了 了解神经营养因子在神经系统中的作用。三 将对问题进行调查以了解具体的、短期的 神经营养因子对突触传递的影响：1)突触是如何传递的 神经营养因子各成员调控的神经元传递 家族？2)神经营养素在突触前或突触后的哪个位点 调节突触传递的作用？3)具体是什么 神经营养因子调节传递的分子机制？这个 拟议的实验将在CA1海马锥体中进行 表达神经营养因子及其受体的神经元 丰富，并作为神经元可塑性的模型被广泛研究。 将使用全细胞膜片钳方法来表征突触 分离的“自体”神经元中的电流--分离的神经元 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人们能够理解 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。

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.