Have you ever wanted to freeze that pesky fruit fly on your kitchen counter? Researchers at the Max Planck Florida Institute for Neuroscience have developed flies that can stop moving when exposed to red light. In this process, they uncovered the specific neural mechanisms at play in halting. Their research, published this week in Nature, highlights insights that extend well beyond just managing fly behavior. The study reveals how the brain activates different neural mechanisms based on the situational context.
The potential of Drosophila in exploring complex behaviors
Stopping is a fundamental action crucial for almost all animal functions. For instance, an animal needs to pause when it finds food and must stop to clean itself when dirty. Although it seems straightforward, the ability to stop is intricately linked to interactions with other behaviors, such as walking.
Dr. Salil Bidaye, a researcher at the Max Planck Florida Institute, specializes in utilizing the remarkably effective research model known as Drosophila Melanogaster (commonly referred to as the fruit fly) to study how neural circuit activity produces specific and complex behaviors, such as maneuvering through their environment. Previously, Dr. Bidaye identified neurons essential for moving forward, backward, and turning, and now he and his team focused on the act of stopping.
“Effective movement in the world relies on stopping at the right moments, just as much as it does on walking. Halting is vital for significant actions like eating, reproducing, and avoiding danger. We sought to explore how the brain manages halting and the scenarios in which halting signals take precedence over walking signals,” explained Bidaye.
Leveraging the advantages of the fruit fly as a research model—including its simplified nervous system, short lifespan, and large number of offspring—Bidaye and his team conducted a genetic screening to pinpoint neurons involved in initiating the stopping action. They employed optogenetics to activate specific neurons by illuminating them with red light, observing which neuron groups triggered halting in freely moving flies.
Two distinct stopping mechanisms
Three unique types of neurons, labeled Foxglove, Bluebell, and Brake, were found to cause the flies to stop when activated. Through meticulous analysis, the researchers discovered that the mechanisms for halting varied based on the specific neuron activated. Foxglove and Bluebell neurons inhibited forward movement and turning, respectively, while Brake neurons suppressed all walking commands and amplified resistance at the leg joints.
“Our research group’s varied expertise was essential in dissecting the precise stopping mechanisms. Each member brought unique perspectives through diverse methodologies like analyzing leg movements, imaging neural activity, and utilizing computational techniques,” Bidaye noted. “Additionally, extensive collaborations across several labs and countries have recently charted the wiring among all the neurons in the fly brain and nerve cord. These connection maps shaped our experimentation and comprehension of the neural circuitry underpinning halting.”
The research team, which included experts from Max Planck Florida, Florida Atlantic University, University of Cambridge, University of California, Berkeley, and MRC Laboratory of Molecular Biology, integrated data from these wiring maps along with various approaches to achieve a comprehensive understanding of the behavioral, muscular, and neurophysiological processes that lead to a fly’s stopping behavior. They observed that triggering these different neurons resulted in distinctive halting methods, which they denominated ‘Walk-OFF’ and ‘Brake’.
The “Walk-OFF” method functions by switching off neurons responsible for walking, akin to taking your foot off a car’s gas pedal. This mechanism, utilized by both Foxglove and Bluebell neurons, depends on the inhibitory neurotransmitter GABA to suppress movement-promoting neurons in the brain.
Conversely, the “Brake” mechanism, executed by the excitatory cholinergic Brake neurons in the nerve cord, actively prevents movement by increasing resistance at the leg joints and ensuring postural stability. This process resembles
stepping on your car’s brakes to halt wheel motion. Like taking your foot off the gas to apply the brakes, the “Brake” mechanism also curbs walking-promoting neurons in addition to preventing movement.
Lead researcher Neha Sapkal expressed the team’s enthusiasm upon uncovering the “Brake” mechanism. “While the ‘Walk-OFF’ method resembles stopping mechanisms identified in other animal models, the ‘Brake’ mechanism is completely novel and leads to a robust halting response in the fly. We were instantly keen to learn how and when the fly employs these unique mechanisms.”
Activation of halt mechanisms based on context
To explore when the flies might use the “Walk-OFF” versus “Brake” strategies, the team employed multiple techniques, including predictive models derived from the wiring diagram of the fly’s nervous system, recording halting neuron activity in the fly, and interrupting mechanisms in a variety of behavioral situations.
The results indicated that both mechanisms were utilized separately in various behavioral contexts and activated by relevant environmental cues. The “Walk-OFF” mechanism was triggered during feeding situations and linked to sugar-sensitive neurons, while the “Brake” mechanism activated during grooming, expectedly influenced by sensory information from the fly’s bristles.
When a fly grooms, it must lift several legs and maintain balance. The Brake mechanism supports this stability by providing resistance at the joints and increasing overall balance for the standing legs. Indeed, when researchers disrupted the ‘Brake’ mechanism, the flies frequently toppled over during grooming.
“The fly brain offers valuable insights into how contextual information activates specific behavioral mechanisms like stopping,” Bidaye said. “We aspire to identify similar context-driven processes in other species. In humans, for instance, when we pause momentarily to adjust our shoes or remove an object from our footwear, we likely engage a stabilizing mechanism akin to that of the Brake mechanism. Understanding context-specific neural circuits and their collaboration with sensory and motor circuits is vital for grasping complex behaviors.”
