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The mesencephalic locomotor region, a region of the brain previously thought to only control walking and other forms of locomotion in vertebrates, also regulates postural changes and other movements, according to a study in mice.
“It was surprising that in this region, which everyone has linked to locomotion, many neurons are not really adapted to locomotion,” said Silvia Arber, PhD, lead author of the study, in a statement from hurry. Arber is group leader at the Friedrich Miescher Institut for Biomedical Research and at the Biozentrum at the University of Basel, Switzerland,
These findings may explain why deep brain stimulation (DBS) of this region led to inconsistent results in people with Parkinson’s disease. DBS in this area of the brain likely influences the activity of separate neuronal populations that control different movements, which can suppress the activity of each other, the researchers noted.
“Therapeutic approaches that target and activate specific neurons could be very effective,” said Arber.
The study, “Functional diversity of bodily actions in the mesencephalic locomotor region, ”Was published in the journal Cell.
Locomotion (movement from one place to another) in vertebrates, especially those moving with two or four limbs on land, is the result of postural control, coordinated recruitment and movement of the limbs, and the effective blocking of limbs. ‘other motor programs not compatible with locomotion.
“These behavioral observations raise the question of the underlying mechanisms of neural circuits involved in the selection and regulation of locomotion and other forms of bodily movement,” the researchers wrote.
The mesencephalic locomotor region, as the name suggests, has been known for decades for its role in controlling walking and other forms of locomotion in several vertebrates. Previous work by Arber’s team has shown that neurons in this region connecting to the spinal cord, an area of the brainstem, are involved in locomotion. The brainstem is the most posterior part of the brain, connecting it to the spinal cord.
However, several studies have suggested that this region may contain neuronal populations with distinct functions.
Now, using cutting-edge techniques to tag, activate, and delete specific populations of neurons in the brains of mice, Arber and his team have provided evidence for the existence of functionally distinct populations of neurons that control different body movements in more locomotion.
They identified, for the first time, two populations of neurons intermingled in the mesencephalic locomotor region: one connecting to the spinal cord and the other to an area of the brain involved in controlling movement called the basal ganglia.
Neurons connected to the spinal cord were highly activated when mice elevated, while those which connected to the basal ganglia were heavily recruited for forelimb behaviors such as grooming and handling objects. Notably, only a few of these neurons were activated during locomotion.
To further confirm the function of these neuronal populations, the team specifically turned on or off each of these populations using a technique called optogenetics, in which brain cells are genetically modified to respond to light.
The light-induced activation of neurons connected to the spinal cord stopped the movement of the mice and led to the forward extension of their head and forelimbs, while their blockage caused the body to shorten for breeding and reduced locomotion speed, possibly due to postural impairment.
Notably, when conditions favored the transition of mice to locomotion, activation of these neurons “induced stretching of the body to at least one full cycle of steps in a fraction of the trials, suggesting that stretching of the body can ease the transition to locomotion, ”the researchers wrote.
These results support a model in which neurons in the mesencephalic locomotor region connecting to the spinal cord are “necessary for postural bodily adjustments necessary for whole-body exploratory behaviors,” while the locomotion-promoting effects rely on the interaction with neurons connecting to the spinal cord, they added.
When the neurons connecting to the basal ganglia were activated, all body movements stalled, while uncoordinated whole body movements were observed after the neuron was removed.
These observations suggest that neurons connecting the basal ganglia in the mesencephalic locomotor region may ‘play a more holistic modulatory role in orchestrating body movements’, and that they may be involved in’ the selection of [suppression] of unselected motor programs, ”the team wrote.
They also noted that, interestingly, the blocking of the ongoing movements induced by the activation of these neurons resembled the freezing episodes of patients with Parkinson’s disease, which may prompt further research into whether the disease affects this neuronal population.
Yet the precise impact of these basal ganglia connecting neurons during behavior cannot be accurately assessed from these type of whole population approaches, the team noted, because each of them has showed variable activation during natural behavior and was never modulated as an entire neuronal population. .
The fact that the mesencephalic locomotor region controls movements and behaviors other than locomotion may also help explain the inconsistent small benefits and many side effects seen when DBS – electrical stimulation of target brain regions – was applied to this region in patients with Parkinson’s disease.
“Our work suggests that targeting the spinal projection [mesencephalic locomotor region] neurons may be beneficial for postural stabilization, while promoting limb gait may require targeting populations with spinal cord projection, ”the researchers wrote. They noted, however, that current DBS technology cannot effectively target only these specific populations.
Next, the team plans to determine the role of the mesencephalic locomotor region in action selection, a process by which the brain chooses to perform a particular movement and suppresses conflicting motor programs.
“It’s exciting that this region controls more than locomotion, so it will be interesting to understand how the neurons we’ve identified interact with other regions of the brain involved in controlling movement,” said Arber.
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