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Researchers visualise motor neurons in real-time on a genetic sub-type level.

When a person walks around the block, their body is mostly on autopilot; they don’t have to consciously think about alternating each step or which muscles it takes to lift a foot and put it back down. That’s thanks to a set of cells in the spinal cord that help translate messages between the brain and the motor neurons, which control muscles.  The nervous system has to make decisions and computations to tell different muscles to contract, or when not to contract, or the amount of force and speed to use when contracting. It’s the collection of cells in the spinal cord, called the locomotor central pattern generator (CPG) that helps make many of these computations, researchers believe. So normal movement requires that CPG neurons in the spinal cord connect to and control when motor neurons fire. However, researchers didn’t know exactly how the CPG cells forged these connections.

Now, researchers at the Salk Institute have developed a method to watch, in real time, the activity of those motor neurons for the first time ever. The team state that the new technology is helping to understand how spinal cord cells make connections with motor neurons, and how neurologists might be able to repair those connections in patients with spinal cord injuries or neurodegenerative diseases.  The opensource study is published in the journal Neuron.

Previous studies have had to rely on electrodes that could detect the change in electrical voltage inside a cell when it’s activated to measure the activity of neurons, whether in the brain or extending throughout the body.  However, it is tricky to use electrodes to simultaneously record the activity of many different neuron types at once to study how their activity is synchronized and follow the pattern of neural network theory, especially on a singular level.

The current study used a fluorescent sensor protein called GCaMP6f that lights up whenever a neuron is activated to improve upon electrode readings. Results show that unlike electrodes, the protein could easily be added to many different cells at once. When the lab added GCaMP6f to motor neurons, they could watch with a microscope which cells were activated in a mouse spinal cord when chemicals that turn on walking circuits were added.  The group note that no post-image processing is needed to interpret this, these raw signals are viewed through the eyepiece of a microscope.

The new method was used in the current study to answer a long-standing question about how the locomotor central pattern generator (CPG), connects to the right motor neurons to allow movements like walking. The team explain that the CPG is where relatively simple signals from the brain, to walk forward, or to move a hand are translated into more complex instructions for motor neurons to control muscles.  Results show that the CPG didn’t rely solely on the cells’ locations to connect to them. Data findings showed the genetic identity of each subtype of cells, what makes those that control the quadriceps muscle different from those that control the calf muscle for instance, is also important.  The group conclude that’s a key finding for research on how to treat spinal cord injuries and ALS.

The team surmise that currently, many researchers are attempting to turn stem cells into motor neurons, which they then implant into the spinal cord to regenerate damaged connections.  They go on to add that their new results suggest that general motor neurons might not do the trick and the best treatment may require precision medicine; the correct genetic subtypes of motor neurons. For the future, the lab state that more work is needed to understand the implications of this revolutionary new method and exactly how it might translate to disease treatment.

Source:  The Salk Institute


Salk scientists were able to selectively add fluorescent proteins to the nuclei of motor neurons (red) using cutting-edge genetic techniques to show how cells in the spinal cord synchronize many neurons at once to allow complex movements. Image: Courtesy of the Salk Institute for Biological Studies.
Salk scientists were able to selectively add fluorescent proteins to the nuclei of motor neurons (red) using cutting-edge genetic techniques to show how cells in the spinal cord synchronize many neurons at once to allow complex movements. Image: Courtesy of the Salk Institute for Biological Studies.

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