Disturb fruit fly larvae with sharp jabs or intense heat and they’ll respond the same way every time. “They always roll two or three times, and then stop rolling and land away from the noxious thing,” says neuroscientist Kazuo Emoto of the University of Tokyo.
Emoto and his team have identified key components of a neural circuit that makes this knee-jerk response to danger possible. The findings, reported in Current Biology, could help inform scientists’ explorations of similar reflexive escape behaviors in other animals, including humans.
Emoto knew there was a specific set of neurons in the larvae’s skin that senses danger. These sensory neurons set off a neural circuit that ultimately triggers the escape behavior. But the chain of other neurons, known as interneurons, that connect those initial sensors to the final response was still largely a mystery.
To identify the key players in the middle of the circuit, the team began by screening about 1,000 strains of Drosophila larvae, each with distinct genetic mutations that caused different groups of neurons to glow fluorescently. They identified one particular group of illuminated interneurons that seemed to reach the sensory neurons projecting from the skin.
They suspected that these interneurons might help link sensory neurons to the motor neurons that trigger muscle movement. So the team systematically tested each link in this hypothesized neural circuit by turning each neuron off and on. They used a combination of neuron silencing, which deactivates neurons by blocking their ability to release neurotransmitters; and optogenetics, which activates neurons by stimulating them with bursts of light.
When they activated the interneurons, the larvae reacted with the escape behavior as though the sensory neurons themselves had been stimulated. When they silenced the interneurons but activated the sensory neurons, the signal was lost and the larvae didn’t roll reliably.
The team then tested whether the neural circuit included a specific set of motor neurons known as SNa neurons. They silenced these motor neurons and then activated either the sensory neurons or the interneurons. In both cases, silencing the motor neurons inhibited the escape response, confirming its key role in the circuit.
“It was a really beautiful study,” says neurogeneticist Dan Tracey of Indiana University, who was not involved in the research. “It definitely helps us to understand at a circuit level how this particular escape behavior is encoded in the nervous system.”
But scientists haven’t closed the loop on this circuit just yet. “This is only the beginning,” says Emoto. “It’s not enough to explain the whole escape behavior.” As Tracey reports in an analysis of recent work in the field, other researchers have identified additional groups of interneurons that also play a role in driving the escape response.
Emoto hopes that piecing together these many potential links in the neural circuitry of the fruit fly brain may eventually inform studies of related but far more complex pathways in human brains. “In the human case, if we touch a very hot plate, we quickly move our hand away, and then we always try to cool down our hand,” explains Emoto. “How this sequence of movements is regulated spatially and temporally, that’s a very open question.”