GENETIC AND MOLECULAR ANALYSIS OF SYNAPTIC PLASTICITY

这项建议的长期目标是阐明负责突触可塑性的分子机制。神经元依赖分子识别线索来引导它们的神经突并选择正确的靶点，这是公认的。虽然在过去的几年里，人们对它们的识别过程有了很多了解，但对控制突触功能可塑性的分子细节却知之甚少。事实上，除了认识到离子通道、细胞内信使和激酶的重要性之外，我们并不真正了解可塑性在体内是如何协调的，以及活动或细胞外信号如何重塑突触乔木。该提案旨在识别和定义突触的活性依赖性结构重塑所需的分子组分。我们希望这些研究能帮助我们勾勒出特定的分子通路，并开始对突触的全面解剖。我们希望这些研究能帮助我们勾勒出特定的分子通路，并开始对体内突触可塑性的全面解剖。我们将集中我们的研究果蝇幼虫的嗅觉感觉神经元和它的中央目标之间的突触。作为遗传筛选的第一步，将建立果蝇幼虫嗅觉系统的标记。这些标记将用于标记选择性神经元及其相应的突触分支，并进行遗传筛选，建立果蝇幼虫嗅觉感觉的标记。这些标记物将用于标记选择性神经元及其相应的突触分支，并对改变特定突触分支特征的显性功能获得和隐性功能丧失突变进行遗传筛选。这些筛选将与突触连接（例如嗅觉线索）中活性依赖性结构变化的测定相结合。我们希望这种多样的方法，结合遗传，分子和生理学方法将有助于阐明突触生物发生和可塑性的基本原则。

The long term goal of this proposal is to elucidate molecular mechanisms responsible for synaptic plasticity. It is well established that neurons rely on molecular recognition cues for guiding their neurites and in choosing their correct targets. While much has been learned about their recognition processes during the last few years, very little is known about the molecular details that govern the functional plasticity of synapses. Indeed, other than appreciating the importance of ion channels, intracellular messengers and kinases, we do not really understand how plasticity is orchestrated in vivo, and how activity or extracellular cues remodel synaptic arbors. This proposal aims to identify and define the molecular components required for activity-dependent structural remodeling of synapses. We hope these studies will help us outline specific molecular pathways, and begin a comprehensive dissection of synapses. We hope these studies will help us outline specific molecular pathways, and begin a comprehensive dissection of synaptic plasticity in vivo. We will focus our studies on the synapse between a Drosophila larval olfactory sensory neuron and its central target. As a first step towards a genetic screen, markers for the Drosophila larval olfactory system will be established. These markers will be used to mark selective neurons and their corresponding synaptic arborizations, and to carry out a genetic screen, markers for Drosophila larval olfactory sensory will be established.. These markers will be used to mark selective neurons and their corresponding synaptic arborizations, and to carry out a genetic screen for dominant gain-of-function and recessive loss-of-function mutations that alter specific synaptic arborization profiles. These screens will be combined with assays for activity-dependent structural changes in synaptic connections (e.g. olfactory cues). We hope this multifarious approach, bringing together genetic, molecular and physiological approaches will help elucidate basic principles of synapse biogenesis and plasticity.