In studying the mating rituals of fruit flies, scientists may have learned something about how brains evolve

Male fruit flies have several tricks for finding a mate, from sensing pheromones in the dark to relying on visual cues in the light.

Now, new research reveals that these tiny suitors are leveraging a flexible network of modular brain circuits to quickly adapt to different mating signals. The study, published in Nature, is the first to describe how diverse species of fruit flies plug new sensory inputs, such as pheromones, into a set of basic brain circuits without needing to develop new neural pathways from scratch.

The findings offer a larger framework for understanding how brain wiring can change to influence behavioral evolution. "The diversity of behaviors across the animal kingdom is enormous, but the underlying mechanisms of how nervous systems are shaped by evolution have been very difficult to unravel," says Vanessa Ruta, head of the Laboratory of Neurophysiology and Behavior. "Here we uncovered what we believe is a key neural mechanism that gives brain circuits the flexibility to rewire across species."

Plug-and-play

One of the great mysteries of behavioral evolution is how, as species diversify, brain circuits keep pace with the rapid changes in social signals that allow individuals to find their ideal mates. Courtship behaviors, for instance, evolve quickly, making it difficult to imagine that the fly brain completely reinvents itself every time a new pheromone enters the Drosophila repertoire.

But until now, it was not possible to identify where evolution acts in the nervous system to alter behavior, and so the key features of what makes such circuits so adaptable remained a mystery. Ruta's group turned to fruit flies, where closely related species share similar brains but rely on vastly different cues for mating rituals. D. simulans, for instance, mainly relies on visual cues to find a mate, while D. yakuba evolved a novel capacity to use pheromones to find a mate even in complete darkness. These and other variations presented an opportunity to study how similar brains detect and perceive different social cues.

"We started looking for parts of the brain that might be primed for flexibility," says Rory Coleman, first author on the study and a postdoctoral fellow in the Ruta lab. "We were searching for features that might make the circuit intrinsically adaptable, potential evolutionary hotspots driving behavioral diversification."

After comparing pheromone-sensing circuits across multiple species-using behavioral assays, genetic tools, neuroimaging, and CRISPR genome editing-they ultimately singled out sensory neurons in the male forelegs and P1 neurons in the higher brain as key to modulating courtship across species. The team found that the basic neural building blocks of male mating behaviors, such as the P1 neurons, are present across species, but different sensory signals can be flexibly wired into this node. This allows fly species to develop different mating strategies without rewiring their entire brains.

For instance, the researchers found that P1 neurons were activated in response to entirely different types of pheromones in D. melanogaster and D. yakuba. Yet the role of P1 neurons in initiating courtship was still conserved across both species. "One important discovery from our work is that there are discrete nodes within the brains of each of these species that can flexibly integrate new sensory modalities," Ruta says. "This flexibility allows conserved nodes like the P1 neuronsRory T. Coleman1, Ianessa Morantte1, Gabriel T. Koreman1, Megan L. Cheng1, Yun
Ding2, Vanessa Ruta1* to still initiate courtship in different species but respond to the distinct cues of their females."

A social brain

This research falls under the umbrella of Rockefeller's Price Family Center for the Social Brain, an initiative focusing on understanding the neuronal, cellular, and molecular foundations of social behavior. In addition to shedding light on flexibility in the face of new sensory inputs, the present work also illustrates an experimental approach for studying how social behaviors evolve across species. "Our results demonstrate that Drosophila is a powerful system for studying behavioral evolution," Ruta says.

By examining how variations in neural circuits shape behaviors like mating, the lab hopes to advance our understanding of the complex interplay between brain function and social behaviors, providing a framework for understanding how social circuits are built to produce adaptive behaviors in the human brain. And while the brain structures of flies and humans differ substantially, it is likely some of the underlying principles of how neural circuits evolve and adapt are conserved across species

"We hope that comparative evolutionary studies like this one will reveal the core rules shaping how neural circuits have been built across the animal kingdom, including in humans," Coleman says. "Many neurological disorders are thought to arise from the miswiring of circuits" Ruta adds. "By examining neural circuits through the lens of evolution, we hope to shed light on which neural motifs can change and how they can be altered, not through the ravages of disease, but as a consequence of evolutionary selection."