Mapping the optic lobes for color vision

描述（由申请人提供）：本提案是5 R 01 EY 017916 -04“色觉视叶标测”的更新。果蝇眼睛收集的视觉信息首先在视叶、视板、视髓和视小叶复合体中处理。髓质是颜色视觉神经网络的第一个中继，但它是运动检测通路的第二步。在上一个授予期，我们已经定义了超过70种细胞类型，这些细胞类型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，可以进行细致的研究，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。我们目前的实验，以了解视神经元的多样性是如何产生的，以及这些神经元如何建立其视网膜连接到光感受器。这将产生知识和工具，然后我们将使用这些知识和工具通过电生理学和行为测定来分析单个神经元在视通路中的功能。三个具体目标将帮助我们实现这些目标。（一）.顺序成神经细胞（NB）转换产生神经元多样性。我们已经发现，产生的NB作为一个波的分化，从髓质神经上皮表达顺序至少三个转录因子的过程中观察到的序列相似的胚胎NB。从这些NB中出现的神经元保持这些基因的表达，并成为不同的细胞类型。我们将确定新的NB和神经元标记物，并确定来自幼虫神经元标记的TF组合的成人神经元细胞类型。（二）、髓质神经上皮的区域化和成神经细胞的特化。顺序产生的NB产生的神经元类型在新月形骨髓外增殖中心（OPC）的不同区域不同。在中央部分，年轻的NB产生局部柱状细胞，保留在它们产生的地方，以及少量的非柱状神经元，迁移到占据它们在整个成人髓质中的视网膜位置。我们将分析NB的谱系如何通过它们沿OPC的沿着位置而被修改。然后，我们将操纵NBs的位置身份和分析的后果上的神经元组成的髓质。因此，我们将定义组合转录因子代码指定髓质神经元类型，并将其与成人的命运。（三）、单个髓质神经元的功能。我们将记录这些神经元对各种光刺激的电生理活动。我们将继续分析参与运动检测的神经元，并扩展对参与色通路的髓质神经元的分析。目标1和2中生成的工具将允许我们通过“交叉”表达来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。 公共卫生相关性：果蝇具有遗传上的顺从性，大脑体积小，但其复杂的行为，已经非常成功地发展成为研究神经回路如何控制行为的模型系统。我们研究如何定义的分子代码，指定延髓神经元和使用电生理学和飞行模拟器，以了解他们的功能，在运动检测和颜色的歧视，视叶的髓质部分的发展和功能。从这个项目中推导出的原理将适用于更复杂的生物体中的其他感觉系统。

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.