A neural circuit that helps flies stay on course

NNavigating the environment is a key skill for many organisms. For years, scientists have wondered how the brain assembles environmental cues, compares them with an animal's desired goal, and guides the organism toward successful navigation. But exploring these questions in the complex mammalian brain has proven difficult.

In two studies published in NatureResearchers from Harvard University and Rockefeller University have peered into the tiny brains of fruit flies to uncover the neural circuitry that performs these calculations. Both research teams described how neurons called PFL3 combine information about the insect's current location with information about its target. While the Harvard University scientists reported how another population of brain cells, anti-target neurons, help the fly correct its path when it strayed far from its target, the Rockefeller University team described a group of neurons that encode information about the insect's target.^1.2 By combining experimental and model-based approaches, these studies reveal a detailed neural circuit that is essential for Drosophila melanogasterThe study examines brain navigation and provides insights into fundamental principles that may govern navigation in more complex brains.

“These behaviors that they're studying, goal-directed control, are universal in navigating animals,” said Daniel Turner-Evans, a neuroscientist at the University of California, Santa Cruz, who was not involved in the studies. “It's just wonderful to see how these behaviors unfold across these different layers and different neurons in the brain and how you can create these really beautiful conceptual and quantitative models that really fit the anatomy and biology.”

In insects, the central complex, a highly conserved conglomerate of brain structures, is key to integrating a variety of sensory inputs and controlling locomotion during navigation. While some neurons in this center act as an internal compass that represents the fly's direction of flight relative to a landmark, others can directly influence an insect's body control.^3.4 By reconstructing the neuronal connections in the brains of various insects, scientists identified the specific communication pathways between different cell types.^5.6 For example, compass neurons communicate with PFL3 neurons.⁷ Two sets of PFL3 cells sit on each side of the fly brain, with neurons in each hemisphere sending projections to the control center on the opposite side. These previous findings suggested that PFL3 cells might allow an insect to directly compare its direction with its target and adjust its flight path to align the two.

In the latest Nature In both studies, the researchers wanted to test this idea experimentally while also studying this navigation circuit in more detail. Both teams recorded neural activity from tethered flies as they ran in a floating sphere. “It basically acts as a treadmill. The fly can run, but because it's a ball, it can also spin,” explains Elena Westeinde, a doctoral student in Rachel Wilson's lab at Harvard University and co-author of one of the studies. In both papers, the researchers placed the spherical treadmill in a virtual reality environment where they presented the fly with a bright bar, a stimulus known to attract insects. The fly ran in a straight line for extended periods of time, allowing the researchers to infer the insect's running direction each time the position of the visual cue changed.

In both studies, the researchers found that PFL3 neurons are involved in controlling the fly's body when it deviates from its intended course. For example, when the fly deviated to the left from its target, PFL3 cells on the right side of the brain activated the insect to correct its course. The opposite was true for PFL3 neurons on the left side.

Because almost all of the input that PFL3 cells receive is shared with another group of neurons called PFL2, Westeinde and her colleagues investigated the role of these cells in the fly's navigation. They found that PFL2 neurons fired strongly when the fly was facing the opposite direction of its target. When the team stimulated these cells, the insect increased its turning speed. “It's like saying, 'No, you're really wrong! You just have to turn around and you'll get closer again,'” Westeinde explained.

At Rockefeller University, Gaby Maimon's team decided to look for cells above PFL3 that encode information about the target. While the fly ran in the spherical treadmill, the researchers rotated the sphere a few degrees and watched certain neurons fire. They found that a group of cells called FC2 did not change their activity when the fly turned in a different direction. To confirm that these cells encoded a representation of the insect's target, Peter Mussells Pires, a postdoctoral fellow in Maimon's lab, and his colleagues stimulated the FC2 neurons optogenetically.[When] Peter stimulated these FC2 target communication neurons, [he] We could make the flies run in different directions,” Maimon explained.

While Maimon's work showed that the FC2 neurons read out the target location, Turner-Evans remains curious about how the insect's brain sets that target. Exploring that question is one of Maimon's next steps. Turner-Evans also believes that exploring how these control signals feed into the complex motor network and are then translated into movements is another important next step.

Even though the fly brain is much simpler than the human brain, its extensive characterization by researchers over the years has made it a powerful system for understanding information processing in the brain. “In the fly, we can uncover these kinds of basic principles that seem to be universal at some level,” Turner-Evans said. “I wouldn't be surprised if some of the conclusions from these studies looking at how these different angular directions and vectors are used to navigate an animal also turn out to be true. [in] mammals.”