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

果蝇鸣叫模式生成的控制：电路机制和感觉调制

• 批准号: 404281558
• 负责人: Dr. Frederic Römschied
• 金额: --
• 依托单位: Department of Molecular Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404281558?language=en
• 关键词: control; song; pattern; generation; Drosophila

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.

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央模式发生器（CPG）。例子包括蝗虫和螃蟹，已经分别确定了驱动飞行和咀嚼的CPG。值得注意的是，在这些实施例中，生理温度用于表征CPG稳健性，揭示了使变温（冷血）动物能够在它们生活的温度下保持生命行为的细胞机制。然而，这些研究局限于可用于监测和操纵神经元活动的工具的范围内，用于神经元识别和操纵的遗传工具的可用性，以及高通量行为实验的可能性，使得果蝇成为研究行为的神经基础的理想对象。此外，果蝇参与复杂的社会行为：在求偶期间，雄性果蝇追逐雌性，同时振动翅膀以产生求偶歌曲。如果这首歌对雌性有吸引力，她会放慢速度以促进交配。最近的证据表明，雄性果蝇动态更新歌曲结构的基础上视觉反馈的女性。虽然基因筛选已经确定了男性的歌曲生产电路的神经元，但我们缺乏歌曲电路的功能特征。特别是，我们不明白神经元活动如何塑造歌曲动力学。此外，我们不知道感觉反馈如何调节歌曲回路的活动，以迅速调整歌曲统计，因此，我将研究如何求爱动态的神经回路的模式化活动的形状：首先，我将分析温度对歌曲动态的影响。这将有助于了解求偶是否在果蝇所经历的温度范围内都是稳健的。我将特别讨论温度如何影响雄性从雌性那里得到的反馈，以及这如何影响他的歌声动力学。其次，我将使用光遗传学激活的歌声回路中的神经元来系统地表征这些神经元对歌声动力学的功能贡献。这将有助于理解单个神经元的模式化活动是如何塑造歌曲的。第三，我将使用闭环光遗传激活（意味着激活是在男性歌曲的某些方面触发的）来评估反馈如何塑造歌曲动力学。这对于理解来自雌性的感官反馈如何被雄性的歌曲回路迅速转化为他的歌曲动力学的变化是很重要的。

项目成果

Flexible circuit mechanisms for context-dependent song sequencing.

• DOI: 10.1038/s41586-023-06632-1
• 发表时间: 2023-10
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Roemschied, Frederic A.;Pacheco, Diego A.;Aragon, Max J.;Ireland, Elise C.;Li, Xinping;Thieringer, Kyle;Pang, Rich;Murthy, Mala
• 通讯作者: Murthy, Mala