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

描述（由申请人提供）：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，是神经科学的基本目标。理解任何给定行为是如何产生的先决条件是了解底层神经回路的组成神经元的身份以及它们之间的突触连接关系。在本申请中，提出将最近在小鼠中开发的第二代GFP跨突触伙伴重建（GRASP）技术适应于果蝇。与具有高假阳性率的GRASP的原始版本不同，GRASP的这种改进版本仅在突触接触位点产生GFP信号。适应这种突触特异性版本的GRASP果蝇将极大地提高映射任何数量的良好表征的果蝇行为的潜在神经回路的能力，从而了解感官信息是如何翻译成行为反应，在这个建立的模型系统具有强大的分子遗传优势。此外，它将有助于阐明神经 果蝇模型的人类医学状况，包括神经退行性疾病，成瘾和睡眠。

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.