Johannes Kohl Untangles the Neural Circuitry Behind Instinct

At Leibniz, Kohl began interrogating the forces that sculpt the neural circuits underlying behaviors in fruit flies, as well as what physiological and environmental factors drive their function. “At first, the circuit seemed mind-blowingly complex, and it would seem quite hopeless to find any functional principles in this tangled mess,” he says. But after he graduated and joined Gregory Jefferis’s Drosophila group at the MRC Laboratory of Molecular Biology in Cambridge, UK, Kohl found that the fruit fly “was a perfect system to investigate the relationship between genetics—how genes wire up circuits—and how these circuits control an animal’s behavior.” 

As a PhD student in Jefferis’s lab, Kohl studied why male and female D. melanogaster display opposite reactions to the male sex pheromone 11-cis-vaccenyl acetate (cVA). To females, cVA is an aphrodisiac, while males respond to the scent with aggression. Combining single-cell electrophysiology in the brains of immobilized fruit flies, high-resolution confocal microscopy, and genetic analysis, Kohl found that both sexes’ peripheral neurons react identically to the pheromone. It is a circuit “switch” the flies have deep inside their brains that leads to sex-specific responses, Kohl explains. The transcription factor fruitless, long implicated in Drosophila sexual behavior, controls the position of specific dendrites and thus wires the circuit in a sex-specific manner. Eliminating the fruitless gene in males leads them to react to cVA as females would, whereas expressing the gene in females masculinizes their behavior, Kohl found.

In the lab, we were making jokes that there were everyone’s standards, and then there were Jonny’s standards. . . . Jonny had breakthroughs all the time.

—Johannes Kohl

By the time he earned his degree in 2013, Kohl was ready to study an animal model other than flies, he says. “Flies are a fantastic model system, but I was looking for a more intriguing behavior.” He chose to do a postdoc with Catherine Dulac, a molecular biologist at Harvard University and Howard Hughes Medical Institute. Dulac’s lab studies mice, and the team had recently discovered that the neuropeptide galanin plays a crucial role in the animals’ parenting behavior. The group’s research had also revealed that galanin is heavily expressed in a region of the hypothalamus called the medial preoptic area (MPOA), and Kohl wanted to explore how this tiny population of neurons orchestrates parenting and other complex behaviors.

“Things like feeding, fleeing, mating, and parenting—in nature, there’s very little room for error in these behaviors,” he says. Tracing the galanin-expressing MPOA neurons showed that they receive signals from 20 different brain areas and are grouped into specific neuronal subsets. Each subset funnels its outputs to a different brain region. By modulating the activity of the specific groups of neurons, Kohl learned that each one seems to be tuned to specific parenting behaviors, such as grooming or interacting with pups.

The research helped Kohl win the Peter and Patricia Gruber International Research Award from the Society for Neuroscience—a $25,000 prize, which he used to help launch his own lab at the Francis Crick Institute in London in January 2019. 

Kohl is now investigating how transient physiological states such as hunger, stress, or tiredness affect the neural circuits underlying parenting, feeding, and aggressive behaviors. There’s no doubt that Kohl will tackle his new work with the same impressive gusto that he applied to his postdoc, Dulac says. “In the lab, we were making jokes that there were everyone’s standards, and then there were Jonny’s standards,” she explains. “Jonny had breakthroughs all the time.” 

Nicoletta Lanese is a former intern at The Scientist. Follow her on Twitter @NicolettaML.