Modulation of Reproductive Behaviour by Neuropeptides in Drosophila

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.