Uncovering Serotonin Secrets in Muscle Movement

Better known for affecting mood, serotonin is also essential for motion. Neuroscientist Sara Fenstermacher of the Simons Society of Fellows explores how the chemical affects motor neurons and why its receptors exist in the spinal cord

Portrait photo of Sara Fenstermacher
Sara Fenstermacher

When Sara Fenstermacher says that she “embodied the liberal arts experience” of fusing the humanities and sciences together, she means it literally. A serious ballet and modern dancer from grade school through college, Fenstermacher ultimately became a neurobiologist studying how the nervous system generates coordinated movements — including the ones she used to perform on stage. Her dance career included stints as a choreographer and performances at Disney World, but Fenstermacher’s parents encouraged her to pursue dance in parallel with her scientific passions.

Fenstermacher began her research career studying the molecular survival mechanisms of axons — the lengthy fibers in a neuron that conduct action potentials to other nerve cells. She is currently investigating how the neurotransmitter serotonin acts on neural circuits in the spinal cord to help generate and regulate the huge range of motor behaviors that humans regularly exhibit. “Movement is the basis of all behavior,” she says, “so it is critical for us to understand the neural pathways that produce movement. And I’m excited that I can incorporate my own movement background into my science.” An edited version of my interview with her follows.

Why does the neuroscience of movement interest you?

We are able to produce an incredibly wide variety of movements that vary greatly in force and speed. I use the example of the winter biathlon, where first the athletes cross-country ski and then they have to stop and pull out the rifle and shoot five very small, distant targets. In one state you’re moving as fast as you can, and in the next you’re relatively still, performing very precise movements to aim and fire your rifle. I’m interested in the circuits in the nervous system that allow you to produce this kind of seamless transition between very different motor states: things that require a little force versus a large force, or low speed versus high speed.

What does serotonin have to do with moving muscles?

Most people associate serotonin with anxiety and depression, but it turns out that serotonin is released all throughout the brain and the spinal cord and can potently change the activity of the circuits that control movement. That’s because serotonin is a neuromodulator: It has the ability to change the rhythm or behavior of single cells in the nervous system. The neuron might fire once every second, and when you add serotonin, it fires 10 times every second. So when serotonin changes the activity of motor neurons that are contacting muscle, you change the contraction rate of the muscle.

Cross section of the mouse spinal cord, outlined by a dashed line, shows serotonin axons (purple) that project from the brain into the spinal cord, densely targeting motor neurons (blue)
Cross section of the mouse spinal cord, outlined by a dashed line, shows serotonin axons (purple) that project from the brain into the spinal cord, densely targeting motor neurons (blue). Credit: Sara Fenstermacher

How did this lead you to look at the spinal cord?

There are two different clusters of serotonin-producing cells. One set projects into the forebrain — these are involved in controlling changes in mood. But a separate set of serotonin cells projects into the spinal cord. Why do we have them, and what are they doing? Well, the spinal cord contains the motor neurons that carry the final “instruction” from the nervous system to the muscle and tells it when to contract. And if you record the activity of these serotonin-producing cells projecting into the spinal cord, you see that they’re firing at a slow rate when you’re walking and at a faster rate when you’re running. Their activity is related somehow to motor activity. How these serotonin cells are communicating with these motor neurons, and adjusting or modulating their activity, is one of the big questions.

How are you investigating this in the lab?

That is literally in progress. We are using optogenetics, which lets us deliver light to a specific population of these serotonin-producing cells in the brain of a mouse and lets us turn the cells off or on during a motor behavior. For example, I can have a mouse run on a treadmill at different speeds: slow, medium and fast. While the mouse is running, I can turn the serotonin cells off or turn them on and see what happens to the mouse’s movement.

Can you imagine any therapeutic applications of this research?

One application, potentially, is in treating spinal cord injuries. Serotonin has the ability to activate the rhythmic patterns of neural activity in the spinal cord: If you throw serotonin on a spinal cord in a dish, you can get those cells to produce a rhythmic pattern of activity that would normally generate walking behavior. If we can understand the details of these serotonin cells and how they influence activity of neurons in the spinal cord, could this be used as a therapeutic in a spinal cord injury, when those inputs from the brain can’t access your spinal cord anymore. My approach to understanding the serotonergic system at a basic-science level — what is the function of serotonin in motor control in the spinal cord? — would surely be able to help in the long term.

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