Linking developmental trajectories to neural circuit function in the Drosophila visual motion detection system

为了形成服务于行为的大脑回路，神经元导航一条从神经前体到功能形态特定回路的发展轨迹。这种发育轨迹如何赋予神经元身份和功能特性，是一个与健康和疾病相关的悬而未决的问题。我们使用果蝇视觉-运动敏感系统来研究这个问题。方向选择性运动敏感的T4/T5神经元是理解(1)如何实现方向选择性以将T4/T5神经元调节到四个基本方向以及(2)相应神经元亚型是如何指定的一个强大的模型。我们实验室的研究结果表明，有必要重新审视目前的范式，将只有四种功能的T4/T5亚型的规范与预定数量的前体细胞分裂联系起来：Hassan实验室展示了瞬时前体细胞扩增，潜在地导致了比预期更多的T4/T5细胞，Silies实验室表明有六种功能亚型编码光学血流模式。总而言之，我们的发现表明，短暂的放大以及随后的功能特化和神经元消除为与行为相关的六种功能类型提供了发育基础。我们将检验这一假设，并阐明发育是如何产生具有功能特性的神经元的。我们的专业知识组合将揭开T4/T5细胞数量和功能特化是如何从不同的祖细胞起始群体中建立起来的时间轨迹。对投射到四个解剖层的六种亚型的功能分析对T4/T5与上下游视流神经元的连接模式进行了具体的预测，这将使用在果蝇中可用的遗传工具和连接学的独特组合来探索。我们的工作将阐明发育机制在多大程度上指导最终调整为服务于动物行为的功能神经回路特性。

To form brain circuits that serve behavior, neurons navigate a developmental trajectory from neural progenitors to functional modality-specific circuits. How this developmental trajectory endows neurons with identity and functional properties is an unsolved problem of relevance to health and disease. We use the Drosophila visual-motion sensitive system to investigate this question. The direction-selective motion-sensitive T4/T5 neurons are a powerful model to understand (1) how direction selectivity is achieved to tune T4/T5 neurons to four cardinal directions and (2) how the corresponding neuronal subtypes are specified. Findings from our labs suggest a need to revisit the current paradigm linking the specification of only four functional T4/T5 subtypes to a predetermined number of progenitor divisions: The Hassan lab demonstrated transient progenitor amplification, potentially leading to more T4/T5 cells than expected, and the Silies lab showed that there are six functional subtypes encoding optic flow patterns. Together, our discoveries suggest that transient amplification followed by functional specialization and neuronal elimination provide a developmental basis for the six functional types relevant for behavior. We will test this hypothesis and elucidate how development generates neurons with functional properties. Our combination of expertise will unravel the temporal trajectory of how the stereotyped T4/T5 cell number and functional specialization is established from a variable starting population of progenitors. Functional analysis of six subtypes projecting to four anatomical layers makes specific predictions about T4/T5 connectivity patterns to upstream and downstream optic flow neurons that will be explored using a unique combination of genetic tools and connectomics available in Drosophila. Our work will elucidate to what extent developmental mechanisms instruct functional neural circuit properties ultimately tuned to serve animal behavior.