Modulation of Reproductive Behaviour by Neuropeptides in Drosophila

在果蝇中，神经系统的性别是由性别决定体系的两个末端基因决定的：无果性(FRU)和双性(DsX)。在发育过程中，Fru和dsx蛋白协同作用，建立性别二态神经回路，专门用于产生性别特有的行为。虽然这些生殖行为本身是遗传的“硬连线”神经回路的产物，但这些行为的显著灵活性在两性中都是显而易见的。这使得雄性和雌性能够改变他们的行为，并在相互竞争的行为之间切换，以响应他们的环境和内部状态。这种能力是由许多调节机制的存在产生的，这些调节机制能够检测和整合内部和外部感觉线索，并相应地改变神经电路功能，从而在电路输出中产生适当的变化。在许多物种中，神经肽是神经网络活动和行为的关键调节器。在黑腹毛虫中，神经肽Sifamide已被证明在调节包括生殖在内的几种行为方面发挥重要作用。例如，雄性体内多肽的敲除会导致它们不仅向雌性求爱，还会向其他雄性求爱。此外，在由fru基因指定的男性特定神经回路中，Sifamide受体的敲除类似地导致对两性的不分青红皂白的求爱。根据这些发现，有人提出，Sifamide可能会调节男性求爱背后的神经回路，以确保只有在适当的环境中才会产生行为，即有接受能力的女性的存在。然而，尽管Sifamide似乎对调节男性求爱很重要，但它实现这一目的的机制仍然难以捉摸。首先，尚不清楚SifAMIDE在相关电路中的作用位置。它可以调节对通常促进或抑制求爱的感官线索的早期检测和处理。或者，Sifamide可以作用于更高级别的决策中心，该中心整合了多感官的外部和内部信息，并选择适当的行为输出。Sifamide还可以调节产生求偶序列的运动神经元的活动。其次，虽然已知该肽通过G蛋白偶联受体发出信号，但该受体下游的细胞通路尚不清楚。因此，尚不清楚Sifamide对神经元活动有什么影响。最后，Sifamide发布的上游事件仍然知之甚少。例如，目前还不清楚是什么触发了多肽的释放，以及它的释放是结构性的还是受特定事件/感官线索的调节。这项工作的最初目的将是调查SIFAMIDE调节雄性求爱行为的机制。这将涉及到使用复杂的遗传工具来定位和操纵已定义的神经元亚组。将这些工具与行为、解剖学和生理学技术相结合，将能够表征Sifamide神经元和求偶电路之间的物理和功能连接，并将阐明多肽调节电路功能以调节行为的机制。通过这样做，这项研究将阐明对许多物种的行为灵活性至关重要的过程。

In Drosophila melanogaster, the sex of the nervous system is specified by two terminal genes of the sex determination hierarchy: fruitless (fru) and doublesex (dsx). During development, Fru and Dsx proteins act in concert to establish sexually dimorphic neural circuits dedicated to the production of the sex-specific behaviours. While these reproductive behaviours are, as such, the product of genetically 'hardwired' neural circuitry, a capacity for significant flexibility in these behaviours is evident in both sexes. This allows males and females to alter their behaviour, and switch between competing behaviours, in response to their environment and internal state. This capacity is engendered by the existence of numerous modulatory mechanisms able to detect and integrate internal and external sensory cues and alter neural circuit function accordingly, producing appropriate changes in circuit output. In many species, Neuropeptides are key modulators of neural network activity and thus behaviour. In D.melanogaster, the Neuropeptide SifAMIDE has been shown to play an important role in regulating several behaviours including reproduction. For instance, knockdown of the peptide in males causes them to display courtship not only towards females but also towards other males. Moreover, knockdown of the SifAMIDE receptor in male specific neural circuitry specified by the fru gene similarly results in indiscriminate courtship toward both sexes. In light of these findings, it has been suggested that SifAMIDE may modulate the neural circuits underlying male courtship to ensure that behaviour is produced only in the appropriate context, I.e. the presence of a receptive female. However, while SifAMIDE appears to be important for regulating male courtship, the mechanisms by which it does so remain elusive. Firstly, it is unclear where SifAMIDE acts within the relevant circuitry. It could modulate the early detection and processing of sensory cues that normally promote or inhibit courtship. Alternatively, SifAMIDE could act on higher order decision making centres that integrate multisensory external and internal information and select appropriate behavioural outputs. SifAMIDE could also modulate the activity of the motor neurons that produce the courtship sequence. Secondly, while the peptide is known to signal through a G protein coupled receptor, the cellular pathways downstream of the receptor are, as yet, uncharacterised. Therefore, it is unclear what affect SifAMIDE has on neuronal activity. Finally, the events upstream of SifAMIDE release remain poorly understood. For example, it is not clear what triggers the release of the peptide and whether its release is constitutive or is regulated by specific events/sensory cues. The initial aim of this work will be to investigate the mechanisms by which SIFAMIDE modulates male courtship behaviour. This will involve the use of sophisticated genetic tools to target and manipulate defined sub sets of neurons. Combining these tools with behavioural, anatomical and physiological techniques will allow physical and functional connectivity between SifAMIDE neurons and courtship circuitry to be characterised, and will elucidate the mechanisms by which the peptide modulates circuit function to regulate behaviour. In so doing, this study will shed light upon a process crucial for behavioural flexibility in many species.