More than just walking: A new role for core brain region

Date:
July 27, 2021
Source:
University of Basel
Summary:
For decades, a key brain area has been thought to merely regulate
locomotion. Now, a research group has shown that the region
is involved in much more than walking, as it contains distinct
populations of neurons that control different body movements. The
findings could help to improve certain therapies for Parkinson's
disease.



FULL STORY ==========================================================================
For decades, a key brain area has been thought to merely regulate
locomotion.

Now, a research group at the Biozentrum, University of Basel, and the
Friedrich Miescher Institut for Biomedical Research (FMI) has shown that
the region is involved in much more than walking, as it contains distinct populations of neurons that control different body movements. The findings could help to improve certain therapies for Parkinson's disease.


==========================================================================
Even the mundane act of walking requires complex movements such as
postural changes and the coordination of all four limbs. Scientists
have known that 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 remained controversial.

By taking a fresh look at the mesencephalic locomotor region, researchers
led by Professor Silvia Arber, a 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.

The findings, published in Cell, call for a rethink of the role of this
key part of the midbrain. "It was surprising that within this region,
which everybody among experts has linked to locomotion, many of the
neurons are not actually tuned to locomotion," Arber says.

Two neuron populations active during body movements but not during
locomotion Working in mice, the researchers used cutting-edge techniques
to label and measure 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 neurons connecting
to the spinal cord increased their activity as the mice reared up,
whereas the other population got active when the animals moved their
forelimbs during behaviors such as grooming or handling objects. But
only a small fraction of these neurons switched on during locomotion,
the researchers found.



========================================================================== Next, the team used a technique called optogenetics, in which brain cells
are genetically engineered to respond to light, to either activate or
silence specific populations of neurons in the mesencephalic locomotor
region. In a set of experiments, the researchers activated the neurons connecting to the basal ganglia as the mice moved around.

As a result, the animals stopped to walk and all body movements stalled.

Instead, 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.

Previous work from the Arber group indicates that neurons from the mesencephalic locomotor region that send their projections to an
area of the brainstem called medulla are involved in the control of
locomotion. The new study suggests 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.

New possibilities in the therapy of people with Parkinson's disease
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. Parkinson's disease is a neurodegenerative condition
that leads to tremor, stiffness, and problems controlling different
movements. An experimental therapy that employs a technique called deep
brain stimulation - - in which electrical impulses are delivered directly
to the mesencephalic locomotor region of people with Parkinson's disease
-- has yielded inconsistent results.

While some patients reported small benefits, others experienced many
side effects. Arber's recent findings suggest why: applying electrical
impulses to all neurons influences the activity of distinct neuronal populations in an uncontrolled manner. A better strategy would be
to stimulate only the neurons that project to the spinal cord or the
medulla, Arber says. "Therapeutic approaches that target and activate
specific neurons could be very successful," she says.

Next, the team plans to investigate the role of the mesencephalic
locomotor region in action selection -- a process through which the brain 'chooses' to perform a particular movement and inhibits conflicting motor programs. "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 says.

========================================================================== Story Source: Materials provided by University_of_Basel. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Manuel J. Ferreira-Pinto, Harsh Kanodia, Antonio Falasconi, Markus
Sigrist, Maria S. Esposito, Silvia Arber. Functional diversity for
body actions in the mesencephalic locomotor region. Cell, 2021;
DOI: 10.1016/ j.cell.2021.07.002 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210727171700.htm

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