Research identifies brain cells that keep mice active

April 11, 2017, The Francis Crick Institute
Research identifies brain cells that keep mice active
GAD65 neurons (green) from the lateral hypothalamus in the brain, surrounded by other lateral hypothalamus neurons (purple). Credit: Christin Kosse, Burdakov Lab

Scientists have discovered a type of brain cell that prevents mice from being overly immobile. The research provides insight into the brain circuits underlying what motivates us to be physically active.

The , called GAD65 neurons, are located in the mouse equivalent of the human . This crucial part of our brain regulates body processes including sleeping and waking, appetite, digestion, body temperature and blood pressure.

The research was led by Denis Burdakov of the Francis Crick Institute and King's College London.

Dr Burdakov says: "If the same neural networks operate in the human lateral hypothalamus, the classic human 'arousal centre', 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's a lot more activity among people who're always at the gym compared to who tend to sit at home in front of the TV."

The team set out to investigate why we, and other mammals, choose to engage in . What makes us walk or run, even when there is no obvious or immediate external reason to do so?

Dr Burdakov explains the background to the research: "Around a century ago, it was proposed that damage to a brain area called the lateral hypothalamus caused people to sit motionless most of the time, with no energy or appetite. It's thought that this brain area emits some essential signals for motivating physical activity. However, it has remained a mystery what these signals are."

Previous research has identified several different types of neuron in the lateral hypothalamus, including cells producing orexin/hypocretin - a key signalling molecule in the brain linked to stress and arousal - and a separate neuronal population called GAD65 cells. The role of GAD65 cells and how they work with orexin was not understood.

To investigate the natural role of the GAD65 cells in brain function and physical activity, the scientists watched when the GAD65 neurons naturally switched on and off in , using a deep-brain recording tool called fiber photometery. They also experimentally silenced the cells to see how this affected the amount of voluntary running by the mice. Both tools used genetics to target the cells very selectively.

The results showed that the cells were activated by orexin and were active right before, and during, bouts of voluntary running. When they silenced the cells, the mice ran a lot less than normal.

In a final experiment, overstimulating the GAD65 cells caused the mice to run around a lot more than usual.

Dr Burdakov says: "These findings shed new light on deep-brain signals that maintain healthy levels of physical activity.

"A next step would be to investigate how the neural circuit described here operates together with other pathways in the that are already known to control voluntary movement and, in this way, promote physical activity in humans."

The paper, Orexin-driven GAD65 network of the lateral hypothalamus sets physical in mice, is published in the Proceedings of the National Academy of Sciences.

Explore further: Origins of 'rage' identified in brain in male animal model

More information: Christin Kosse et al. Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1619700114

Related Stories

Origins of 'rage' identified in brain in male animal model

February 11, 2016
Violent, unprovoked outbursts in male mice have been linked to changes in a brain structure tied to the control of anxiety and fear, according to a report by researchers from NYU Langone Medical Center to be published in ...

Gamma oscillations coordinate food seeking

February 2, 2017
Food seeking is a crucial survival instinct. However, until recently, little was known about how the brain regulates this behavior. Scientists at the Leibniz-Institut für Molekulare Pharmakologie (FMP) and NeuroCure Cluster ...

3 p.m. slump? Why a sugar rush may not be the answer

November 16, 2011
(Medical Xpress) -- A new study has found that protein and not sugar activates the cells responsible for keeping us awake and burning calories. The research, published in the 17 November issue of the scientific journal Neuron, ...

Neuronal activity shows link between wakefulness and fight-or-flight response in mice

July 15, 2016
Researchers centered at Nagoya University revealed a role for orexin neurons of the hypothalamus in regulating the response to harmful stimuli in mice. Painful stimuli activated orexin neurons, except in mice that were anesthetized. ...

Increased production of neurons in hypothalamus found in mice fed high fat diets

March 26, 2012
(Medical Xpress) -- A research team made up of people from a wide variety of biological sciences has found that mice fed a diet high in fat tend to see an increase in the number of neurons created in the hypothalamus, a region ...

Recommended for you

How do we lose memory? A STEP at a time, researchers say

March 23, 2018
In mice, rats, monkeys, and people, aging can take its toll on cognitive function. A new study by researchers at Yale and Université de Montréal reveal there is a common denominator to the decline in all of these species—an ...

Brain's tiniest blood vessels trigger spinal motor neurons to develop

March 23, 2018
A new study has revealed that the human brain's tiniest blood vessels can activate genes known to trigger spinal motor neurons, prompting the neurons to grow during early development. The findings could provide insights into ...

Being hungry shuts off perception of chronic pain

March 22, 2018
Pain can be valuable. Without it, we might let our hand linger on a hot stove, for example. But longer-lasting pain, such as the inflammatory pain that can arise after injury, can be debilitating and costly, preventing us ...

From signal propagation to consciousness: New findings point to a potential connection

March 22, 2018
Researchers at New York University have discovered a novel mechanism through which information can be effectively transmitted across many areas in the brain—a finding that offers a potentially new way of understanding how ...

Using simplicity for complexity—new research sheds light on the perception of motion

March 22, 2018
A team of biologists has deciphered how neurons used in the perception of motion form in the brain of a fly —a finding that illustrates how complex neuronal circuits are constructed from simple developmental rules.

Focus on early stage of illness may be key to treating ALS, study suggests

March 22, 2018
A new kind of genetically engineered mouse and an innovation in how to monitor those mice during research have shed new light on the early development of an inherited form of amyotrophic lateral sclerosis (ALS).


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.