A recent study uncovers deep-brain signaling in a new type of neuron that controls voluntary physical movement.
More than a hundred years ago, it was discovered that damage to a certain brain area caused people to remain immobile and listless, and lose appetite. This led researchers to believe that brain signals in the lateral hypothalamus (LH) - the area connected with immobility - might control physical activity.
However, the precise mechanism behind this association remained unknown - until now. New research uses cutting-edge technology to explore what causes physical (in)activity in mammals and finds a new type of brain cell in the LH that triggers voluntary movement when activated.
The study was carried out by researchers at King's College London in the United Kingdom, who were led by Prof. Denis Burdakov from the Centre for Developmental Neurobiology at the Institute of Psychiatry, Psychology and Neuroscience.
The findings were published in the journal PNAS.
Studying motor neurons in the lateral hypothalamus
Using optogenetic brain circuit analysis and deep-brain recording, the researchers examined the equivalent of the LH in mice.
Optogenetics is a newly developed technology that uses light to track and control the activity of cells. The cells are first genetically modified to become sensitive to a certain light frequency, and then they can be activated or silenced, enabling researchers to examine brain circuits more precisely.
Deep-brain recording is a method that involves inserting stimulating electrodes deep into the subcortical areas of the brain. The method is used to study and record the neurons responsible for movement, as well as being a potential treatment for movement disorders.
For this study, the researchers used a deep-brain recording technique called fiber photometry.
Orexin-activated GAD65 neurons control voluntary movement
Using these methods in mice revealed new types of brain cell called GAD65 neurons. These neurons are a subset of cells located in the LH, but they are molecularly different from the other neurons that have previously been associated with movement control.
Additionally, the study found that these new brain cells are activated by orexin - a peptide that usually serves to signal stress and appetite.
More specifically, the researchers examined when the GAD65 cells would switch on and off, and they observed that these cells were active when the mice engaged in voluntary running, as well as immediately before that.
The researchers also selectively silenced and activated these cells to see how they affected the mice's drive to run. When the cells were deactivated, the mice ran significantly less than usual.
Finally, Burdakov and team overstimulated the cells, which made the mice run a lot more than normal.
Findings may explain why some people exercise more than others
"These findings shed new light on deep-brain signals that maintain healthy levels of physical activity," the authors conclude.
The study's lead researcher also comments on the significance of these findings:
"If the same neural networks operate in the human lateral hypothalamus, the classic human 'arousal center,' our findings could shed light on how the brain chooses between activity and inactivity, including the health implications of this choice. You could imagine 'pointing' an MRI machine to look at this area of the brain, for example, and see if there is a lot more activity among people who are always at the gym compared to [those] who tend to sit at home in front of the TV."
Prof. Denis Burdakov
Prof. Burdakov also outlines directions for future research, saying that: "A next step would be to investigate how the neural circuit described here operates together with other pathways in the brain that are already known to control voluntary movement and, in this way, promote physical activity in humans."