The mesencephalic locomotor region, which is part of the midbrain, is involved in regulating walking and other forms of locomotion in many animal species. But the function of neurons in this area of the brain remains controversial. Researchers led by Silvia Arber, PhD, a professor and group leader at the FMI and the Biozentrum of the University of Basel, have characterized distinct populations of neurons that are involved in movements other than walking.

Their findings are published in the journal Cell, and titled “Functional diversity for body actions in the mesencephalic locomotor region.”

“The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion,” wrote the researchers. “Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson’s disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements.”

Working in mice, the researchers labeled and measured the activity of different populations of excitatory neurons in the mesencephalic locomotor region. The team discovered two intermingled populations of neurons—one sending neuronal projections down to the spinal cord, and another connecting in the opposite direction to parts of a brain area called basal ganglia.

The researchers used optogenetics to activate the neurons connecting to the basal ganglia as the mice moved around. The researchers observed the animals stopped to walk and all body movements stalled. When the researchers switched on the neurons that project to the spinal cord as the mice stood still, the animals extended their head and forelimbs forward. Only in some cases, after extending their body, the rodents started to walk. When these neurons were silenced, the researchers observed opposite behavioral responses.

The new findings suggested that those that connect directly to the spinal cord are instead involved in regulating body extension and postural changes, which are likely essential for initiating locomotion.

Besides upending a long-standing idea about the role of the mesencephalic locomotor region, the study could also have implications for easing postural and gait problems in people with Parkinson’s disease who do not respond to drugs.

The researchers look forward to investigating the mesencephalic locomotor region in action selection. “It’s exciting that this region controls more than locomotion, so it will be interesting to understand how the neurons we identified interact with other brain regions involved in movement control,” Arber said.

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