GENETIC AND MOLECULAR ANALYSIS OF SYNAPTIC PLASTICITY

本研究的长期目标是阐明突触可塑性的分子机制。神经元依赖分子识别线索来引导其神经突并选择正确的目标，这已经得到了很好的证实。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是如何在体内协调的，以及活性或细胞外信号是如何重塑突触支架的。本研究旨在鉴定和定义突触活动依赖性结构重塑所需的分子成分。我们希望这些研究将帮助我们勾勒出特定的分子途径，并开始对突触进行全面的解剖。我们希望这些研究能够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进行全面的解剖。我们将重点研究果蝇幼虫嗅觉感觉神经元与其中心靶点之间的突触。作为基因筛选的第一步，果蝇幼虫嗅觉系统的标记将被建立。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标记。这些标记将用于标记选择性神经元及其相应的突触断裂，并对改变特定突触断裂谱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（如嗅觉线索）中活动依赖性结构变化的测定相结合。我们希望这种多种多样的方法，将遗传学，分子和生理学的方法结合起来，有助于阐明突触生物发生和可塑性的基本原理。

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.