From genes to behavior: genetic dissection of visual circuitry usingDrosophila melanogaster

这项提议的目的是阐明基因如何控制视觉行为。我们专注于识别一种特定视觉反应背后的神经回路。接下来将详细描述这些神经回路中已识别的细胞类型的发育和功能。我们的方法将使我们更好地理解神经回路是如何对一个特定的视觉行为进行基本计算的。我们使用果蝇黑腹果蝇作为一个强大的分子遗传模式生物。像许多昆虫以及一些脊椎动物一样，果蝇可以探测入射光的e矢量方向，通常被称为偏振。在自然界中，偏振光是通过大气散射以及从有光泽的表面（如水）反射而产生的。事实证明，这两种刺激对许多动物都很重要，它们可以作为一种刺激，提高它们的导航技能，或者引导它们前往繁殖地点。我们将三个实验目标结合在一起：首先，我们将从基因上识别那些对线偏振光的行为反应至关重要的细胞类型（Aim I）。行为分析和基因筛选的结合将用于识别那些计算偏振视觉关键步骤的神经元。从这些细胞单位的集合中，极化视觉电路将被组装起来，使用在果蝇中首创的分子遗传学工具。针对这些感兴趣的细胞类型的遗传系将作为这些电路元件功能表征的基础（见下文）。其次，我们将可视化已识别的电路元件在体内的电活动（Aim II）。基因诱导，荧光钙传感器将用于可视化识别细胞类型对偏振光的功能反应特性，在行为的动物。结合体内电路中断工具（细胞类型的失活，过度激活）将揭示细胞在电路中的计算作用。在不同的国际合作中，这些研究将扩展到使用电生理学。第三，我们将研究视觉回路中已识别细胞类型的转录谱（Aim III）。为了实现这一目标，我们将使用最先进的技术，如damID和RNAseq。这些研究将揭示形成极化视觉电路中细胞类型功能特性的转录景观，以及定义其身份的转录因子代码。这个项目将与该系的Claude DESPLAN教授密切合作进行。他是纽约大学生物学专业的教授。总之，我们的目标是对神经回路如何驱动特定视觉行为进行细胞描述。我们的发现将为正在进行的运动视觉和颜色辨别的研究提供协同的见解。

The goal of this proposal is to elucidate how genes control visual behaviors. We focus on identifying those neural circuits underlying one specific visual response. This will be followed by a detailed characterization of the development and function of identified cell types within these neural circuits. Our approach will lead to a better understanding of how basic computations are performed by neural circuits with respect to one specific visual behavior. We use the fruitfly Drosophila melanogaster as a powerful molecular genetic model organism. Like many insects, as well as some vertebrates, Drosophila can detect the e-vector orientation of incident light, commonly known as polarization. In nature, polarized light is created through athmospheric scattering, as well as through reflection from shiny surfaces, like water. Both stimuli have proven important for many animals, by serving as a stimulus improving their navigational skills, or by guiding them towards sites of reproduction. We are combining three experimental aims: First, we will genetically identify those cell types crucial for the behavioral response to linearly polarized light (Aim I). A combination of behavioral assays and genetic screens will be used to identify those neurons computing critical steps in polarization vision. From this collection of cellular units, the polarization vision circuit will be assembled, using molecular genetic tools pioneered in Drosophila. The genetic lines targeting these cell types of interested will serve as a basis for the functional characterization of these circuit elements (see below). Secondly, we will Visualize the electrical activity of identified circuit elements in vivo (Aim II). Genetically inducible, fluorescent Calcium sensors will be used to visualize the functional response properties of identified cell types to polarized light, in the behaving animal. A combination with in vivo circuit breaking tools (inactivation, over-activation of cell types) will then reveal the cells computational roles within the circuit. In different international collaborations, these studies will be extended towards using electrophysiology. Thridly, we will investigate the transcriptional profiles of identified cell types in the visual circuit (Aim III). To achieve this goal we will use state-of-the-art techniques like damID and RNAseq. These studies will reveal the transcriptional landscape shaping the functional properties of cell types within the polarization vision circuit, as well as the transcription factor code defining their identities. This project will be performed in close collaboration with Prof. Claude DESPLAN, at the Department. of Biology, at New York University. In conclusion, we aim for a cellular description of how neural circuits drive specific visual behaviors. Our findings will provide synergistic insight for ongoing studies on motion vision and color discrimination.