Scientists Unveil New Ways by Which Motor Neurons Talk to Muscles in Response to Changes

The communication between motor neurons and muscles, which allow us to control our movements, is more dynamic than previously thought, a new study with zebra fish shows.

Researchers at the Karolinska Institutet in Sweden discovered that adult motor neurons can switch their messenger, or neurotransmitter, in response to increased physical activity or spinal cord injury to enhance motor function.

These findings open up new possibilities for restoring motor control in patients with spinal cord injuries or certain motor nerve diseases, including amyotrophic lateral sclerosis (ALS).

The study, “Adult spinal motoneurons change their neurotransmitter phenotype to control locomotion,” was published in the journal Proceedings of the National Academy of Sciences of the United States of America.

Voluntary control of our muscles occurs through communication between motor neurons and muscle cells at a specific location called the neuromuscular junction. Here, neurons transfer the neurotransmitter acetylcholine, which makes muscle cells contract.

Malfunction in the contact zone between the neuron and muscle cell, called a synapse, where acetylcholine is released, has been linked to many neurodegenerative diseases, including ALS.

Traditionally, it has been thought that the release of neurotransmitters is fixed and determined early during development, and adult motor neurons are believed to release only acetylcholine.

Increasing evidence suggests that neurons may be able to switch between different neurotransmitters. However, these changes were considered beyond the abilities of motor neurons due to their key role in controlling behavior.

To tackle the question of how motor neurons react to changes, Karolinska researchers used a small freshwater fish model called a zebra fish.

They found that an increase in physical activity, through forced swim training, or injury to the spinal cord can redirect a pool of adult motor neurons to switch from producing and releasing acetylcholine to another neurotransmitter called glutamate.

The switch coincided with an enhancement of the animal’s locomotor system — the fish were able to swim faster.

“Our study shows that the function of the neuromuscular synapses can change under certain conditions and in certain diseases in order to fine-tune movements, which was a completely unexpected finding,” Konstantinos Ampatzis, PhD, an assistant professor in the Department of Neuroscience at Karolinska and the study’s lead author, said in a press release.

While additional studies are required to understand how a subset of motor neurons can acquire the ability to secrete glutamate, these findings open the door for potential new strategies to treat diseases linked with impaired communication at the neuromuscular junction, such as ALS and spinal muscular atrophy (SMA).

“Our study can open new doors to the treatment of diseases involving reduced neuromuscular transmission,” Ampatzis said. “More detailed knowledge on which neurons express specific neurotransmitters can enable the development of better treatments that restore function to the nervous system.”