High-Energy Motion Activates Nearly All Neurons in Fruit Fly Brain, Study Finds
Simons Collaboration on the Global Brain investigators and their colleagues imaged a large portion of the fruit fly brain as the insect performed various activities. The findings may expand the standard perception of the fly brain as a genetically hardwired system to one that includes considerable flexibility.
Attempting to understand the thoughts of a fruit fly is a quest bordering on science fiction. Recent research explores how and why the entire fruit fly brain becomes more active during periods of physical activity, a general phenomenon spanning species from flies to mice. In turn, it may one day reveal how our own brains function.
The study, published on September 11, 2023, in Nature Communications, sought to understand both where and for how long neurons are active in the brain, as well as why neural activity extends beyond neurons specialized for a given behavior.
In the research, Simons Collaboration on the Global Brain (SCGB) investigator Evan Schaffer of the Icahn School of Medicine at Mount Sinai and his colleagues used an emerging microscopy technique to collect 3D neural data at single-cell resolution across a central swath of the fruit fly brain. They collected the data as the flies performed various behaviors — walking, grooming, bending and doing nothing.
Their analysis shows that the neural activation during large movements such as walking extends all the way down to single cells in the fruit fly, Drosophila melanogaster. Previously, scientists assumed that the fruit fly’s brain circuitry consisted of hardwired collections of microcircuits. The new research showed that neurons also have the flexibility to control or be controlled by the fly’s current behavioral state.
“We posit that multiple neural pathways may benefit from the fly’s current state, or, in short, it is good to know what you are doing,” says Schaffer, who worked on the project while at Columbia University. “Flippancy aside, we wanted to know at the large scale — but with simultaneous resolution at the smallest scale — what happens in the brain when a fruit fly does something simple like walking.”
The textbook modular Drosophila brain circuitry is based on previous identification of specific neurons or clusters of neurons corresponding to highly specific behaviors like mating or egg laying. The new study revealed that even a simple locomotive behavior like running involves the activation of nearly all neurons, even those in microcircuits specific to egg laying.
“The most interesting finding was that the brain is organized on so many different levels in space and time,” says Schaffer. “At the large scale, any energy-intensive behavior seems to activate the whole brain at two different timescales. There were large chunks of the brain that track what the fly is doing right now and other chunks that track what the fly did recently, regardless of what it is currently doing.”
The experimental design involves suspending a fly under a microscope. A Styrofoam ball is brought just within reach of the fly’s legs, forming a spherical treadmill for the fly to walk on while the researchers record neural activity with a technique called swept, confocally aligned planar excitation (SCAPE) microscopy. When the ball is removed, the fly flails. Both running and flailing induce brainwide activity, while less vigorous behaviors like grooming or simply sitting do not.
“We also observed organization at many scales, all the way down to just two cells — one on each side of the brain — performing the same computation not obviously related to behavior,” says Schaffer. “I tend to anthropomorphize this as saying the fly is thinking.”
Previous studies in mice have shown that the entire brain becomes more active during motion. This has been demonstrated for fruit flies, too, but not at sufficiently small-scale resolution. Such detail is important because fruit flies are an ideal system for studying the mechanism and function of brainwide neural activity. While the fruit fly brain is simple relative to that of a mouse or a human, there is enough complexity to extract fundamental principles underlying how the brain works, Schaffer says.
“The central dogma in fly neuroscience is that the brain is a genetically hardwired system,” he says. “We have recapitulated previous findings correlating motion and brain activity in mice, but we did so in flies, and we are the first to show at single-cell resolution that large-scale locomotive activity extends all the way down to single cells in the fruit fly brain.”
Schaffer and colleagues also discovered that when the dominant activity associated with an observable behavior like running is removed from the neural data, a complex landscape spanning time and space emerges for almost all neurons. In this landscape, termed ‘residual activity,’ diverse neurons display complex patterns of activity with no apparent dependence on the locomotive state. This global state of motion likely provides a context that benefits other brain computations.
“There’s this dichotomy between a rigid system and one that’s more flexible,” says Schaffer. “It is not that the whole brain is driving the behavior but rather that the whole brain is aware of what is happening. For instance, the part of the brain thinking, ‘Where am I going to find my next meal?’ is getting feedback about ‘Am I moving right now?’ That changes the way we think about how the brain works at a very basic level.”
Knowledge of the current behavioral state can also regulate future behavior. Neural activity feeds back on behavior to create a loop where what has been done recently impacts what will be done at some later time. This means it may truly be beneficial to know what you are doing, especially during bouts of physical activity.
Principles governing how the brain works and how it is interconnected with the body remain uncertain. However, practices that combine mind and motion can be traced back thousands of years. While modern medicine commonly divides the cognitive from the physical, ancient philosophers may have had it right all along. “Although the human brain looks nothing like the fly brain, it’s a reasonable extrapolation that exercise affects cognition, even in a fruit fly,” says Schaffer.
Running and meditation are associated with improved cognition and sensory perception, among other mental and physical health benefits. This integration of mind and body is an active focus of scientific inquiry in subjects from humans to mice to even the lowly fruit fly. “There are many ways in which the body affects the brain,” says Schaffer. “And increasingly as a field, we are finding that it is essential to look at the body to understand how the brain works.”
“Understanding fundamental aspects underlying the complex circuitry of the brain will be critical to treat or cure any number of diseases,” he says.
