Adaptation of a synapse-specific version of GFP Reconstitution Across Synaptic Pa

描述(申请人提供)：了解生物体如何从其环境中提取感觉信息，将其编码为电信号和化学信号，然后整合和处理这些信号，以产生有利于生存的行为反应，这是神经科学的基本目标。要理解任何特定行为是如何产生的，一个先决条件是了解潜在神经回路的组成部分神经元的身份以及它们之间的突触连接关系。在这一应用中，建议适应于果蝇，即最近在小鼠身上开发的第二代GFP跨突触伙伴重建(GRASP)技术。与假阳性率很高的原始版本GRASH不同，这种改进版本的GFP只在突触接触部位产生GFP信号。将这种突触特异性版本的GRAP适应果蝇将极大地提高绘制任何数量具有良好特征的果蝇行为的潜在神经回路的能力，从而理解在这个具有强大分子遗传优势的已建立的模型系统中，感觉信息是如何转化为行为反应的。此外，它将有助于阐明神经 包括神经退行性疾病、成瘾和睡眠在内的人类健康状况的果蝇模型背后的回路。

DESCRIPTION (provided by applicant): Understanding how organisms extract sensory information from their environment, encode it into electrical and chemical signals, then integrate and process these signals to produce behavioral responses conducive to survival, is a fundamental goal of neuroscience. A prerequisite for understanding how any given behavior is generated is knowledge of both the identities of the component neurons of the underlying neural circuit and the synaptic connectivity relationships among them. In this application it is proposed to adapt to Drosophila the second-generation GFP Reconstitution Across Synaptic Partners (GRASP) technique recently developed in the mouse. Unlike the original version of GRASP that had a high false-positive rate, this improved version of GRASP produces GFP signals exclusively at synaptic contact sites. Adaptation of this synapse-specific version of GRASP to Drosophila will tremendously enhance the ability to map the underlying neural circuits of any number of well-characterized Drosophila behaviors and thereby the understanding of how sensory information is translated into behavioral responses in this established model system with powerful molecular genetic advantages. In addition, it will be useful for eluciding the neural circuitry underlying Drosophila models of human medical conditions including neurodegenerative disease, addiction, and sleep.