Communication Between Stem Cell Derived Motor Neurons, Muscle Cells Measured

Researchers have developed a novel system to measure communication between stem cell–derived motor neurons and muscle cells in a Petri dish.

In a proof of principle, they have shown that functional motor circuits can be created outside the body using stem cell–derived neurons and motor cells, and that the level of communication, or synaptic activity, between them can be accurately measured by stimulating the motor neurons with an electrode and then tracking the transfer of electrical activity into the muscle cells to which the neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells. This allows calcium and other ions to enter the cells, causing them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons.

The estimation could shed light on a variety of neurodegenerative diseases, such as spinal muscular atrophy and amyotrophic lateral sclerosis (Lou Gehrig's disease), in which communication between motor neurons and muscle cells is thought to unravel, said, Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."
 
Novitch said the synaptic communication activity his team was able to create and measure using muscle cells and motor neurons derived from mouse embryonic stem cells looks very similar to what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases," he added.

"To do that, we had to first define an activity profile of normal synaptic communication. Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

Adapted from the UCLA announcement.