Stop! Neural Mechanisms for Halting Identified – Neuroscience News

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Summary: Scientists have identified two neural mechanisms, “Walk-OFF” and “Brake,” that control stopping behavior in fruit flies. Using optogenetics, they activated specific neurons to halt fly movement under red light.

These mechanisms are context-dependent, with “Walk-OFF” controlling stopping during feeding and “Brake” during grooming. This discovery enhances understanding of how the brain manages movement and could inform future studies on neural processes in other animals.

Key Facts:

  • Two neural mechanisms, “Walk-OFF” and “Brake,” control stopping in flies.
  • Neurons activated by red light halt fly movement in real-time.
  • The mechanisms are context-specific, depending on behaviors like feeding or grooming.

Source: Max Planck Institute

Ever wish you could stop that fruit fly on your kitchen counter in its tracks?

Scientists at Max Planck Florida Institute for Neuroscience have created flies that halt under red light. In doing so, they discovered the precise neural mechanisms involved in stopping.

Using optogenetics to activate specific neurons by shining a red light, the researchers turned on small groups of neurons to see which caused freely walking flies to stop. Credit: Neuroscience News

Their findings, published this week in Nature, have implications far beyond controlling fly behavior. They demonstrate how the brain engages different neural mechanisms depending on environmental context. 

The power of Drosophila to understand complex behaviors 

Halting is a critical action essential for almost all animal behaviors. When foraging, an animal must stop when it detects food to eat; when dirty, it must stop to groom itself. The ability to stop, while seemingly simple, has not been well understood as it involves complex interactions with competing behaviors like walking. 

Max Planck Florida scientist Dr. Salil Bidaye is an expert in using the powerful research model Drosophila Melanogaster (aka the fruit fly) to understand how neural circuit activity leads to precise and complex behaviors such as navigating through an environment.

Having previously identified neurons critical for forward, backward, and turning locomotion, Dr. Bidaye and his team turned to stopping. 

“Purposeful movement through the world relies on halting at the correct time as much as walking. It is central to important behaviors like eating, mating, and avoiding harm. We were interested in understanding how the brain controls halting and  where halting signals override signals for walking,” said Bidaye.  

Taking advantage of the fruit fly’s power as a research model, including the animal’s simplified nervous system, short lifespan, and large offspring numbers, Bidaye and his team used a genetic screen to identify neurons that initiate stopping.

Using optogenetics to activate specific neurons by shining a red light, the researchers turned on small groups of neurons to see which caused freely walking flies to stop. 

Two mechanisms for stopping 

Three unique neuron types, named Foxglove, Bluebell, and Brake, caused the flies to stop when activated. Through careful and precise analysis, the scientists determined that the flies’ stopping mechanisms differed depending on which neuron was active.

Foxglove and Bluebell neurons inhibited forward walking and turning, respectively, while Brake neurons overrode all walking commands and enhanced leg-joint resistance. 

“Our research team’s diverse expertise was critical in analyzing precise stopping mechanisms. Each team member contributed to our understanding by approaching the question through different methods, including leg movement analysis, imaging of neural activity, and computational modeling,” credits Bidaye.

“Further, large research collaborations spanning multiple labs and countries have recently mapped the connections between all the neurons in the fly brain and nerve cord. These wiring diagrams guided our experiments and understanding of the neural circuitry and mechanisms of halting.” 

The research team, consisting of scientists from Max Planck Florida, Florida Atlantic University, University of Cambridge, University of California, Berkeley and the MRC Laboratory of Molecular Biology, combined the data from the wiring diagrams and these multiple approaches to gain a holistic understanding of the behavioral, muscular, and neuronal mechanisms that induced the fly’s halting.

They found that activating these different neurons did not stop the flies in the same way but used unique mechanisms, which they named ‘Walk-OFF’ and ‘Brake’. 

As the name implies, the “Walk-OFF” mechanism works by turning off neurons that drive walking, similar to removing your foot from the gas pedal of a car. This mechanism, used by the Foxglove and Bluebell neurons, relies on the inhibitory neurotransmitter GABA to suppress neurons in the brain that induce walking.  

The “Brake” mechanism, on the other hand, employed by the excitatory cholinergic Brake neurons in nerve cord, actively prevents stepping by increasing the resistance at the leg joints and providing postural stability.

This mechanism is similar to stepping on the brake in your car to actively stop the wheels from turning. And just as you would remove your foot from the gas to step on the brake, the “Brake” mechanism also inhibits walking-promotion neurons in addition to preventing stepping. 

Lead researcher on the project Neha Sapkal, describes the team’s excitement in discovering the “Brake” mechanism.

“Whereas the ‘Walk-Off’ mechanism was similar to stopping mechanisms identified in other animal models, the ‘Brake’ mechanism was completely new and caused such robust stopping in the fly. We were immediately interested in understanding how and when the fly would use these different mechanisms.”  

Context-specific activation of halt mechanisms  

To determine when the fly might use the “Walk-OFF” and “Brake” mechanisms, the team again took multiple approaches, including predictive modeling based on the wiring diagram of the fly nervous system, recording the activity of halting neurons in the fly, and disrupting the mechanisms in different behavioral scenarios.  

Their findings suggested that the two mechanisms were used mutually exclusively in different behavioral contexts and were activated by relevant environmental cues.

The “Walk-OFF” mechanism is engaged in the context of feeding and activated by sugar-sensing neurons. On the other hand, the “Brake” mechanism is used during grooming and is predicted to be activated by the sensory information coming from the bristles of the fly.  

During grooming the fly must lift several legs and maintain balance.  The Brake mechanism provides this stability through the active resistance at joints and increased postural stability of the standing legs. Indeed, when the scientists disrupted the ‘Brake’ mechanism, flies often tipped over during grooming attempts. 

“The fly brain has provided insight into how contextual information engages specific mechanisms of behaviors such as stopping.”

Bidaye says, “We hope understanding these mechanisms will allow us to identify similar context-specific processes in other animals. In humans, when we stop and lift our foot to adjust our shoe or remove a stone from our tread, we are likely taking advantage of a stabilizing mechanism similar to the Brake mechanism.

“Understanding context-specific neural circuits and how they work together with other sensory and motor circuits is the key to understanding complex behaviors.” 

Funding: This research was supported by DFG- German Research Foundation, the Carl Angus DeSantis Foundation, the Wellcome foundation and the Max Planck Florida Institute for Neuroscience. This content is solely the authors’ responsibility and does not necessarily represent the official views of the funders. 

About this motor control and neuroscience research news

Author: Lesley Colgan
Source: Max Planck Institute
Contact: Lesley Colgan – Max Planck Institute
Image: The image is credited to Neuroscience News

Original Research: Open access.
Neural circuit mechanisms underlying context-specific halting in Drosophila” by Salil Bidaye et al. Nature


Abstract

Neural circuit mechanisms underlying context-specific halting in Drosophila

Walking is a complex motor programme involving coordinated and distributed activity across the brain and the spinal cord. Halting appropriately at the correct time is a critical component of walking control.

Despite progress in identifying neurons driving halting, the underlying neural circuit mechanisms responsible for overruling the competing walking state remain unclear.

Here, using connectome-informed models and functional studies, we explain two fundamental mechanisms by which Drosophila implement context-appropriate halting.

The first mechanism (‘walk-OFF’) relies on GABAergic neurons that inhibit specific descending walking commands in the brain, whereas the second mechanism (‘brake’) relies on excitatory cholinergic neurons in the nerve cord that lead to an active arrest of stepping movements.

We show that two neurons that deploy the walk-OFF mechanism inhibit distinct populations of walking-promotion neurons, leading to differential halting of forward walking or turning.

The brake neurons, by constrast, override all walking commands by simultaneously inhibiting descending walking-promotion neurons and increasing the resistance at the leg joints.

We characterized two behavioural contexts in which the distinct halting mechanisms were used by the animal in a mutually exclusive manner: the walk-OFF mechanism was engaged for halting during feeding and the brake mechanism was engaged for halting and stability during grooming.

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