What Happens in the Neuron Doesn’t Stay in the Neuron

The role of serotonin in overcoming depression

By Peter M. Vishton, PhDWilliam & Mary
Edited by Kate Findley and proofread by Angela Shoemaker, Wondrium Daily

You’ve probably heard of SSRIs like Zoloft and Prozac that are used to treat depression. How do they actually work, though? Professor Vishton explains.

Woman crying with her hands in her face
A particular neurotransmitter called serotonin has been found to be at low levels in the brains of people suffering from depression. Photo By Marjan Apostolovic / Shutterstock

What Is Serotonin?

Researchers have found that arousal—that is, interrupting your brain’s state of equilibrium—can help one to overcome depression. One theory for how this might be implemented in the brain is via the production of different neurotransmitters. Serotonin is a chemical produced in the brain that enables neurons to communicate with one another.

The basic components of neuronal activities have been called the action potential. Neuronal cells all possess a resting electrical potential of about negative 70 millivolts. 

If you were to place a tiny electrode inside a neuron and another one just outside that same neuron, there would be a voltage difference—like a very weak battery. That voltage difference is very consistently around negative 70 millivolts for every neuron in your entire body.

Periodically, a neuron produces an action potential starting near the part of the neuron called the cell body. The voltage spikes from this negative 70 millivolts, to around positive 40 millivolts, and then back down again to negative 70 millivolts.

This pulse of electrical activity propagates down the length of the axon portion of the neuron until it reaches its terminals, or the ends. Within these terminals are storage sites referred to as synaptic vesicles. Every time an action potential reaches one of these axon terminals, some of these vesicles burst open, and they release the neurotransmitter that’s stored within them.

The Post-Synaptic Neuron

The neurotransmitter is released into something called the synapse; this is a microscopic gap between one neuron and the next. The neurotransmitter diffuses across that gap and adheres to receptor sites on a neighboring neuron. 

“I call this—the second neuron—the post-synaptic neuron,” Professor Vishton said. “As the neurotransmitter adheres to the surface of that postsynaptic neuron, it influences the likelihood that it will produce an action potential of its own.”

Different neurons contain different types of neurotransmitters. Some are excitatory—that is, the more of the neurotransmitter that is released, the more likely a postsynaptic neuron action potential is. 

Some neurotransmitters are inhibitory. That is, the more of this inhibitory neurotransmitter that’s released into the synapse, the less likely a postsynaptic action potential is.

Reuptake and Serotonin

There is one last step in this neuronal communication process that’s worth considering here—reuptake. Our brains invest a lot of energy in producing those neurotransmitters. 

Rather than using them once and then discarding them, neurons recycle the neurotransmitter. After the neurotransmitter is released from those synaptic vesicles, it gets sucked back up into the synaptic vesicles; if the action potentials of a neuron slow down enough or stop entirely the amount of neurotransmitter in the synapse itself will quickly drop down close to zero.

One particular neurotransmitter that’s been implicated in theories of depression is called serotonin. The brains of people suffering from depression tend to have relatively low levels of serotonin. This is based in part on some clever neuroimaging technology.

Rather than focusing a scanner on blood flow or the anatomical structure of a brain region, a positron emission tomography scanner (known as a PET scanner) can be tuned to concentrations of various neurotransmitters—neurotransmitter receptors, actually—in different parts of the brain. People who suffer from major depression have substantially fewer serotonin receptors in their midbrain than do non-depressed control participants.

The midbrain is a region that contains the hypothalamus and the limbic system—a part of the brain associated with emotion and mood regulation, so this makes a lot of sense. It seems that the part of the process that leads to depression involves a reduction in the sensitivity of these regions to serotonin.

SSRIs and Neurotransmitters

The best evidence for the serotonin theory of depression is the effectiveness of a variety of serotonin-specific drugs. Zoloft® and Prozac® are the two most famous members of a whole family of drugs that function as selective serotonin reuptake inhibitors—commonly these are called SSRIs.

As described, during the reuptake process, the neurotransmitter is released into the synapse and then reabsorbed into the presynaptic neuron’s vesicles for storage and later release. These drugs interfere with that reuptake process. 

Thus, the serotonin is released into the synapse, where it has its normal effect. However, instead of being stopped a few moments later by the reuptake process, the serotonin is left right there in the synapse. 

Over time, this greatly magnifies the effect of any action potential. It effectively strengthens the connections between those midbrain neurons. Thus, as the theory goes, it reduces the symptoms associated with depression.

This article was edited by Kate Findley, Writer for Wondrium Daily, and proofread by Angela Shoemaker, Proofreader and Copy Editor for Wondrium Daily.
Image of Professor Peter Vishton

Peter M. Vishton is an Associate Professor of Psychology at William & Mary. He earned his PhD in Psychology and Cognitive Science from Cornell University. Before joining the faculty of William & Mary, he taught at Northwestern University and served as the program director for developmental and learning sciences at the National Science Foundation.