Mapping the optic lobes for color vision

描述（由申请人提供）：该提案是5R01EY017916-04“映射色觉的光学叶”的更新。果蝇眼睛收集的视觉信息首先在视叶、视板、视髓质和视小叶复合体中进行处理。髓质是色觉神经网络的第一个中继，但它是运动检测路径的第二步。在之前的授权期内，我们已经定义了超过70种细胞类型，这些细胞在投射到小叶复合体之前形成重叠的视网膜定位图。由于髓质包含有限数量的神经元和连接，我们可以对这些神经元和连接进行细致的研究，因此我们可以解决有关复杂神经结构的发育和功能的基本问题。我们提出的实验，以了解如何产生视觉神经元的多样性，以及这些神经元如何建立他们的视网膜连接到光感受器。这将产生知识和工具，我们将使用这些知识和工具通过电生理学和行为分析来分析单个神经元在视神经通路中的功能。三个具体目标将帮助我们实现这些目标。（1）. 序贯神经母细胞（NB）转换产生神经元多样性。我们发现，从髓质神经上皮分化产生的NBs，其顺序表达至少三种转录因子，其过程与胚胎NBs中观察到的序列相似。从这些NBs中产生的神经元保持这些基因的表达，并成为不同的细胞类型。我们将鉴定新的NB和神经元标记物，并鉴定由tf组合标记的幼虫神经元衍生的成体神经元细胞类型。（2）. 髓质神经上皮的区域化和神经母细胞的特化。在月牙形髓质外增殖中心（OPC）的不同区域，顺序生成的NBs所产生的神经元类型不同。在中央部分，年轻的NBs既产生局部柱状细胞，并保留在它们产生的地方，也产生少量的非柱状神经元，这些非柱状神经元迁移到整个成年髓质中占据其视网膜位置。我们将分析NBs的谱系如何随着它们在OPC上的位置而改变。然后，我们将操纵NBs的位置身份，并分析其对髓质的神经元组成的影响。因此，我们将定义指定髓质神经元类型的组合转录因子代码，并将其与它们的成年命运联系起来。(3)。单个髓质神经元的功能。我们将记录这些神经元在各种光刺激下的电生理活动。我们将继续分析参与运动检测的神经元，并将这一分析扩展到参与颜色通路的髓质神经元。目标1和目标2中生成的工具将允许我们通过“交叉”表达沉默或刺激这些神经元，以使用我们的飞行模拟器分析苍蝇的运动和颜色行为。

DESCRIPTION (provided by applicant): This proposal is a renewal of 5R01EY017916-04 "Mapping the optic lobes for color vision". Visual information gathered by the Drosophila eye is first processed in the optic lobes, lamina, medulla and lobula complex. The medulla is the first relay in the neural network for color vision, but it is the second step in the motion detection pathway. In the previous granting period, we have defined over 70 cell types that form overlapping retinotopic maps before projecting to the lobula complex. Because the medulla contains a finite number of neurons and connections that can be studied in exquisite detail, we can address fundamental questions about the development and function of a sophisticated neural structure. We present experiments to understand how optic neuron diversity is generated and how these neurons establish their retinotopic connections to photoreceptors. This will produce knowledge and tools that we will then use to analyze the function of individual neurons in optic pathways through electrophysiology and behavior assays. Three specific aims will help us reach these goals. (1). Sequential neuroblast (NB) switching generates neuronal diversity. We have discovered that the NBs generated as a wave of differentiation from the medulla neuroepithelium express sequentially at least three transcription factors in a process similar to the sequence observed in embryonic NBs. The neurons emerging from these NBs maintain expression of these genes and become different cell types. We will identify new NB and neuronal markers and identify the adult neuronal cell types derived from larval neurons marked by combinations of TFs. (2). Regionalization of medulla neuroepithelium and specialization of neuroblasts. The types of neurons generated by the sequentially generated NBs differ in distinct regions of the crescent shaped medulla Outer Proliferation Center (OPC). In the central part, young NBs produce both local columnar cells that remain where they were generated, as well as a smaller number of non-columnar neurons that migrate to occupy their retinotopic position in the entire adult medulla. We will analyze how the lineage of NBs is modified by their position along the OPC. We will then manipulate the positional identity of NBs and analyze the consequence on the neuronal composition of the medulla. We will thus define the combinatorial transcription factor code specifying medulla neuron types and will relate it to their adult fates. (3). Function of individual medulla neurons. We will record electrophysiological activity of these neurons in response to various light stimuli. We will continue our analysis of neurons involved in motion detection and extend this analysis of medulla neurons involved in chromatic pathways. The tools generated in aims 1 and 2 will allow us to silence of stimulate these neurons through 'intersectional' expression to analyze the motion and color behavior of flies using our flight simulator. PUBLIC HEALTH RELEVANCE: Drosophila, with its genetic amenability and the small size of its brain, yet its sophisticated behavior, has been very successfully developed as a model system to study how neural circuits control behavior. We investigate how the medulla part of the optic lobes develop and function by defining the molecular code that specifies medulla neurons and use electrophysiology and a flight simulator to understand their function in motion detection and color discrimination. The principles deduced from this project will be applicable to other sensory systems in more complex organisms.