Research in mice identifies neurons that control locomotion

Date:
January 20, 2022
Source:
Cell Press
Summary:
For more than a century, scientists have known that while the
commands that initiate movement come from the brain, the neurons
that control locomotion once movement is underway reside within
the spinal cord.

Researchers now report that, in mice, they have identified one
particular type of neuron that is both necessary and sufficient
for regulating this type of movement. These neurons are called
ventral spinocerebellar tract neurons (VSCTs).



FULL STORY ==========================================================================
For more than a century, scientists have known that while the commands
that initiate movement come from the brain, the neurons that control
locomotion once movement is underway reside within the spinal cord. In a
study published January 20 in the journal Cell, researchers report that,
in mice, they have identified one particular type of neuron that is both necessary and sufficient for regulating this type of movement. These
neurons are called ventral spinocerebellar tract neurons (VSCTs).


==========================================================================
"We hope that our findings will open up new avenues toward understanding
how complex behaviors like locomotion come about and give us new
insight into the mechanisms and biological principles that control this essential behavior," says the paper's senior author George Mentis,
associate professor of pathology and cell biology in the Department
of Neurology at Columbia University. "It's also possible that our
findings will lead to new ideas for therapeutic avenues, whether they
involve treatments for spinal cord injury or neurodegenerative diseases
that affect movement and motor control." VSCTs were discovered in the
1940s, but researchers have long believed that their main function was
to relay messages about neuronal activity from the spinal cord to the cerebellum. The new study reports that instead they control locomotor
behavior both during development and in adulthood.

"These findings were a huge surprise," Mentis says. "One of the key
discoveries in our study was that apart from their connection to the cerebellum, these neurons make connections with other spinal neurons that
are also involved in locomotor behavior via their axon collaterals."
The research involved several novel experimental approaches. One part
of the research used optogenetics, employing LED light to regulate
certain proteins that were expressed selectively in VSCTs to either
activate or suppress the neuronal activity. Another set of experiments
used chemogenetics, a process by which a chemical compound is used to
activate or suppress synthetic ligands expressed artificially in these
neurons, controlling their activity.

Leveraging the ability of intact spinal cords from newborn mice to
function in a dish, the researchers showed that activation of VSCTs by
light induced locomotor behavior. When VSCT activity was suppressed
by light or by drugs, ongoing locomotor behavior was halted. During
adulthood, freely moving mice stopped moving when the activity of VSCT
was suppressed by injecting an inhibitory drug. Locomotor behavior was
also tested by the ability of mice to swim. Mice were unable to swim and
simply floated in the water when VSCTs were silenced. In all of these
models and experiments, the researchers demonstrated that VSCTs alone
were both necessary and sufficient for controlling locomotor activity -- activating them was enough to induce activity while suppressing them
was enough to stop it.

Mentis acknowledges that there are limitations to conducting this type
of research in mice, including the fact that while humans are bipedal,
mice are quadrupedal; thus, their locomotion could be regulated in a
different way. But he notes that other research on neurodegenerative
diseases and processes in mice has led to clinical trials in human
patients, suggesting that these findings are also likely to be applicable.

For their next steps, the team plans to identify and map precisely the
neuronal circuits that VSCTs make with motor neurons and other spinal
neurons. They also would like to identify select genetic markers and
uncover potential subpopulations of VSCTs and explore their role in
different modes of locomotion. Finally, they plan to explore how
the function of VSCTs is altered in the context of pathology and neurodegenerative diseases.

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========================================================================== Journal Reference:
1. Joshua I. Chalif, Mari'a de Lourdes Marti'nez-Silva, John
G. Pagiazitis,
Andrew J. Murray, George Z. Mentis. Control of mammalian locomotion
by ventral spinocerebellar tract neurons. Cell, 2022; 185 (2):
328 DOI: 10.1016/j.cell.2021.12.014 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220120125407.htm

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