The control of song pattern generation in Drosophila: Circuit mechanisms and sensory modulation

了解神经系统如何产生复杂的行为是非常具有挑战性的：我们必须了解哪些神经元产生行为，它们如何控制肌肉活动，以及感觉反馈如何调节这些神经元的活动。为了解决这个问题，以前的研究集中在相对较小的神经系统上，这些神经系统有助于识别驱动行为的中枢模式发生器（cpg）。例如蝗虫和螃蟹，它们的CPGs分别驱动飞行和咀嚼。值得注意的是，在这些例子中，生理温度被用来表征CPG的稳健性，揭示了使恒温动物（冷血动物）在其生活的温度下保持重要行为的细胞机制。然而，这些研究在可用于监测和操纵神经元活动的工具范围内受到限制。神经识别和操作的遗传工具的可用性，以及高通量行为实验的可能性，使果蝇黑腹果蝇成为研究行为神经基础的理想对象。此外，果蝇也有复杂的社会行为：在求偶期间，雄蝇在追逐雌蝇的同时振翅发出求偶之歌。如果这首歌对雌鸟有吸引力，它会放慢速度以促进交配。最近的证据表明，雄性果蝇根据来自雌性的视觉反馈动态地更新鸣叫结构。虽然基因筛选已经确定了雄性歌曲产生回路的神经元，但我们缺乏歌曲回路的功能特征。特别是，我们不了解神经元活动是如何影响歌曲动态的。此外，我们不知道感官反馈如何调节歌曲电路的活动，以便快速调整歌曲统计。因此，我将研究如何通过神经回路的模式活动来塑造求爱动态：首先，我将分析温度对歌曲动态的影响。这将有助于了解在果蝇所经历的温度下，求偶行为是否稳健。我将特别讨论温度如何影响雄性从雌性接收到的反馈，以及这如何影响它的歌声动态。其次，我将使用光遗传学激活的神经元在歌唱电路系统地表征这些神经元的功能贡献的歌曲动力学。这将有助于理解歌曲是如何被单个神经元的模式活动所塑造的。第三，我将使用闭环光遗传激活（意味着激活在雄性歌曲的某些方面被触发）来评估反馈如何塑造歌曲动态。这对于理解来自雌性的感官反馈是如何被雄性的鸣叫回路迅速转化为其鸣叫动态的变化是很重要的。

Understanding how nervous systems generate complex behaviors is incredibly challenging: We have to understand which neurons generate behavior, how they control muscle activity, and how sensory feedback modulates the activity of these neurons.To approach this problem, previous studies have focused on comparatively small nervous systems that facilitate identification of central pattern generators (CPGs) that drive behavior. Examples include the locust and the crab, for which the CPGs driving flight and chewing, respectively, have been identified. Notably, in these examples physiological temperature was used to characterize CPG robustness, revealing cellular mechanisms that enable ectothermic (cold-blooded) animals to maintain vital behaviors across the temperatures they live in. Yet, these studies were limited in the range of tools available to monitor and manipulate neuronal activity.The availability of genetic tools for neuronal identification and manipulation, and the possibility of high-throughput behavioral experiments, render the fruit fly Drosophila melanogaster an ideal subject for studies of the neural basis of behavior. Also, fruit flies engage in complex social behaviors: During courtship, the male fly chases the female while vibrating his wing to produce courtship song. If the song is attractive to the female, she will slow down to facilitate mating. Recent evidence suggests that male flies dynamically update song structure based on visual feedback from the female. While genetic screens have identified neurons of the male’s song-production circuit, we lack a functional characterization of the song circuit. In particular, we do not understand how neuronal activity shapes song dynamics. Further, we do not know how sensory feedback modulates activity of the song circuit in order to rapidly adjust song statistics.I will hence study how courtship dynamics are shaped by patterned activity of neural circuits:First, I will assay the influence of temperature on song dynamics. This will help to understand whether courtship is robust across the temperatures fruit flies experience. I will particularly address how temperature influences the feedback the male receives from the female, and how this affects his song dynamics.Second, I will use optogenetic activation of neurons in the song circuit to systematically characterize the functional contribution of these neurons to song dynamics. This will help to understand how song is shaped by patterned activity of individual neurons.Third, I will use closed-loop optogenetic activation (meaning the activation is triggered on certain aspects of the male’s song) to assess how feedback shapes song dynamics. This will be important to understand how sensory feedback from the female is rapidly transformed by the male song circuit to changes in his song dynamics.