Peptides control the fruit fly after mating via command neurons

Scientists have identified neurons within the brain of a female fruit fly that respond to signals from the male during mating.

Male fruit flies transfer a substance called sex-peptide during mating into the seminal fluid along with the sperm. This sex pheromone affects the behavior of the female fly, so she will start laying eggs and will be less inclined to mate further.

This is a common phenomenon in insects, but until now, it was not known where in the nervous system the neurons that drive these so-called ‘post-mating behaviours’ are located.

Researchers at the University of Birmingham have now found a way to identify which specific groups of neurons in the fly brain were responding to the sex peptide. To achieve this scientific discovery, they attached the sex peptide pheromone, which normally circulates in the blood of insects, to the outside of the neurons.

Now, if this cell-membrane-bound sex-peptide is expressed in neurons that also express the receptor for the sex-peptide, it will induce post-mating behavior. In this way, they were able to find where in the brain the neurons that sense the sex peptide are located. Their results are published today in eLife.

To understand how the brain responds to the sex peptide, the team investigated the genetic framework of key genes involved in determining sex. These genes direct male or female differentiation.

Unlike many other genes, sex-determining genes are very complex. The research team, led by Dr Matthias Soller, reasoned that the regulatory regions of these genes could be broken down to be expressed in far fewer neurons.

In addition, the team found an additional genetic trick that allowed them to cross two or even three expression patterns. Using this trick, they were able to direct the expression of the membrane-bound sex peptide in just a few neurons. Using this information, the team was able to map several distinct areas within the female brain that caused behavioral changes in the presence of the male sex peptide.

Interestingly, the researchers found that the neurons targeted by the sex-peptide belonged to a higher-order group called ‘command neurons’, which are essential for behavioral decision-making. This contrasts with earlier theories that the peptides affected sensory neurons, which operate at a lower, reflexive level.

They also found that the peptide affected more than one set of command neurons. The team identified at least five different groups of neurons involved in the process, making it possible that the male sex peptide interferes with female action selection at several different levels.

Lead author Dr Mohanakarthik Nallasivan, from the University of Birmingham’s School of Biosciences, said: “This work will help us understand how behavior is encoded in the brain and how sensory information is translated into action signals. Reproductive behaviors are networked in the brain, rather than learned behaviors, so if we can understand this behavioral pathway, we may be able to influence it, for example by limiting the ability of mosquitoes to find hosts.”

Lead author Dr Matthias Soller, from the University of Birmingham, added: “The Drosophila brain is the first where all the neurons have been cataloged and the synaptic connections have been mapped. We now have the resources available to uncover the neural basis of these behaviours. Like the sequencing of the first genomes, Drosophila paved the way for the sequencing of the human genome, and here we have the same thing: research in Drosophila is guiding how we can get the architecture of the human brain.

“This pioneering work has implications for increasing our understanding of how our brains work, particularly those behaviors that are ‘hard-wired’ or hard-wired into our neural circuitry.”

But although the pathways through which the male sex peptide manipulates female behavior are now clearer, the female fruit fly can still bypass these behavioral instructions. For example, if she is not physically strong or if the environmental conditions are not suitable for egg laying, she will modify her behavior accordingly.

This research will serve as a key paradigm, helping researchers resolve some of the most fundamental questions about brain architecture and function, including decision-making processes.