Despite the pivotal role of motor neurons in movement, how a single motor neuron contributes to control during movement remains unclear. Measuring the activity of individual neurons in moving animals has proven to be experimentally difficult.

However, advances have made it possible for researchers to manipulate single motor neurons in fruit flies as the insects move freely. A new study presents the findings from the characterization of the individual roles of the motor neurons that control head movement in Drosophila melanogaster.

The findings were published in Nature in the paper, “Motor neurons generate pose-targeted movements via proprioceptive sculpting.

“This is one of the first times scientists have analyzed in 3D what single motor neurons do while the body moves naturally,” said Stephen Huston, PhD, associate research scientist at Columbia Univeristy’s Zuckerman Institute. “You can’t understand how the brain makes the body move without knowing what each motor neuron does, just as you can’t understand how a puppeteer makes a marionette move without understanding what the puppet strings do.”

In experiments that began at the Howard Hughes Medical Institute’s Janelia Research Campus, the first step for the researchers was to activate light-sensitive molecules in the 25 or so motor neurons that control head movements of the fly. This enabled the scientists to use a red light to switch on motor neurons one at a time. At the same time, they recorded the resulting head motions while using artificial intelligence techniques to track these movements.

“Most neurons act in concert as a population, so we didn’t expect to see much or even any head movement at all when we activated just one motor neuron at a time,” Huston said.

At most, the scientists had expected that each single motor neuron was hardwired to produce one simple motion—for instance, making the head turn left 10 degrees. Instead, through computational analysis later performed at the Zuckerman Institute, the researchers discovered that activating each motor neuron could make the head rotate in a variety of ways, some even in opposite directions from each other, depending on the starting posture of a fly’s head.

More specifically, the team writes, “We find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron.”

They added that a feedback model “predicts that this convergent behavior results from motor neuron drive interacting with proprioceptive feedback” and they went on to “identify and genetically suppress a single class of proprioceptive neuron that changes the motor neuron-induced convergence as predicted by the feedback model.”

Pinpointing what the brain does on the cellular level in fruit flies is more than just an academic exercise. “A better understanding of what motor neurons do can help us understand diseases that affect the motor system, such as amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease,” Huston said.

Next the researchers want to investigate how other kinds of neurons in the fly, such as those in the visual system, interact with motor neurons to control movement.

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