Messengers of the Brain

1
Introduction

Real Human Brain Exhibit
The behavior of neurotransmitters - the messengers of the brain - affects both mind and body. Matt Candy / Getty Images

You're taking Prozac, and you've heard it described as an SSRI. Maybe you know that SSRI stands for selective serotonin reuptake inhibitor. But that's quite a mouthful - what does it mean?

Terms like selective serotonin reuptake inhibitor, monoamine oxidase inhibitor, and serotonin norepinephrine reuptake inhibitor all describe how a particular medication functions. These three are abbreviated as SSRI, MAOI, ​and SNRI, and all are types of antidepressants.

In order to make sense of any of this, it is necessary to understand something about how impulses are transferred from one nerve to the next since medications such as mood stabilizers, antidepressants, and antipsychotics all affect this process to bring about changes.

In this article, I will give a simplified description of how the brain's message carriers (neurotransmitters) operate, and then try to clarify the process by telling the illustrated story "GABAs on the Move."

Note: Other antidepressants and types of psychiatric medications have different sorts of names that may reflect their chemical composition (for example, tricyclic antidepressants), what they're used for (anticonvulsants) or a combination of factors (typical and atypical antipsychotics, which are, respectively, older and newer drugs treating psychosis).

2
Neurotransmitters

Synapse, vesicles, receptors, terminal button, axon and enzyme
Figure 1: The elements controlling neurotransmitters. © Marcia Purse

There are several neurotransmitters, but the ones that are most related to mood disorders like bipolar disorder are:

Other neurotransmitters include acetylcholine, which transmits orders to the muscles; and histamine, which has a lot to do with allergies, appetite regulation, weight gain (for those on certain medications) and sleep quality.

When a message comes in at one end of a nerve cell, an electrical impulse travels down the "tail" of the cell (axon) and causes the release of the appropriate neurotransmitter. Molecules of the neurotransmitter are sent into the tiny space between nerve cells, called the synaptic cleft. There, one or more of the following can occur for each molecule:

  1. It may bind (attach) to the receptors in the adjacent nerve cell, send the message on, leave the receptor, then repeat this process or go on to one of the other steps.
  2. It may hang around in the synapse until a receptor becomes available, bind to it, release and continue with steps 1 to 3 until its activity is ended by steps 4, 5 or 6.
  3. It may bind to the first cell's autoreceptors, which tell that cell not to release any more of the neurotransmitter molecules, then leave the autoreceptor and continue trying to bind again somewhere until its activity is ended by step 4, 5 or 6.
  4. It may be rendered inactive by an enzyme.
  5. It may be reabsorbed by the first cell in the "reuptake" process, and recycled for later use or deactivated.
  6. It may diffuse out of the synapse and be deactivated elsewhere.

Don't get too bogged down in the terminology here. 

3
Why Neurotransmitters Might Not Work Right

Molecules of neurotransmitters and the human brain
When something interferes with the normal functioning of neurotransmitters, there can be profound effects, both mentally and physically. Stockbyte / Getty Images

Now, so many things can go wrong with this process that it's not surprising mood disorders are fairly common. For example:

  • The nerve cells (neurons) might not be manufacturing enough of a neurotransmitter.
  • Too many neurotransmitter molecules may be dissolved or deactivated by enzymes.
  • Too much of a neurotransmitter may be released.
  • The molecules may be reabsorbed too quickly by the reuptake transporters.
  • The autoreceptors may be activated too soon, shutting down the release of neurotransmitter molecules prematurely.

Channels that are influenced by electrically charged particles, such as potassium, sodium, chloride or calcium, are also involved in regulating the process. It's enough to make your head hurt, isn't it?

4
Communication at Brain Complex (or "GABAs on the Move")

A call is received by the motor pool
Transformation of Figure 1 (left) to Figure 2: The office buildings of "Brain Complex". © Marcia Purse

For our story, let's change the components shown above into something more familiar - parts of a neighborhood. The two neurons are Building A (top) and Building B (bottom) of Brain Complex. They are separated by a narrow street (the synapse or synaptic cleft).

The GABA terminal button from Figure 1 is now a motor pool. Each vesicle containing neurotransmitter molecules becomes a minibus filled with GABA Team messengers. The receptors and autoreceptor become phone booths. The reuptake transporter, where neurotransmitters are sucked back in to be recycled, changes to an inviting coffee shop. And the enzymes are assassins on motorcycles. (No offense meant to motorcycle lovers!)

So up in Building A, the driver of each minivan gets a call from the front office (that's the upper neuron's cell body, not shown) on his cell phone: "Send this message over to Building B!" And right away things start to happen.

5
The Messenger Neurotransmitters Take Off

The vesicles release neurotransmitters into the synaptic cleft
Figure 3: The motor pool (vesicles) release neurotransmitters (messengers) into the synaptic cleft (street) between buildings (neurons). © Marcia Purse

Immediately the drivers take their vehicles (that is, vesicles) to the garage exit and release the GABA Team messengers (neurotransmitters) into the street (synaptic cleft) between Building A (the sending neuron) and Building B (the receiving neuron). Like sprinters, the GABAs take off quickly, each looking for a phone booth that matches his or her uniform (they could not get into any other color booth).

Gertrude, Gerald, and Gloria get there first. Quickly each slips into a booth (receptor) and makes a call into the office (cell body) of Building B, relaying the message. Then each backs out into the street (synapse) and looks for another booth. All the GABA messengers are elbowing each other out of the way (and dodging motorcycles) to get into the available booths and make the same call if they get in.

6
Things Can Go Wrong for Neurotransmitters

Autoreceptors, enzymes, receptors and reuptake transporters
Figure 4: George GABA can't do his job, and Gary gets distracted. © Marcia Purse

But there are some traps and hazards for the GABA team. George GABA never makes it to Building B at all -- he has been knocked unconscious by a motorcycle-riding assassin (enzyme). His color change denotes that he has forgotten the message now - in essence, he has been "deactivated." If too many messengers are hit by motorcycle assassins, not enough of them will survive to pass the message to Building B, the receiving nerve cell.

Meanwhile, Glenn GABA has gone to the phone booth attached to Building A. "There's too many of us out here," he tells the front office. "Don't send any more." Still, he then goes back out into the street toward Building B's phone booths. Only when the front office gets enough calls like Glenn's are the minivan drivers told to return to the motor pool and not send any more messengers out. If many GABAs make this same call too soon, too few messengers may be sent from Building A. If too few GABAs call in, there may be way too many messengers visiting the phone booths (receptors) of Building B.

And then there is that seductive coffee shop (reuptake transporter) on the other corner of Building A. If a messenger like Gary here gets close enough to smell the heavenly aroma of fresh coffee and doughnuts, he or she will surely be sucked in, and once inside, will be refreshed and then return to the motor pool to await the next assignment. While eventually all the surviving GABAs will return home via the coffee shop, if it's having a special on chocolate doughnuts, too many messengers may head to the shop before completing their jobs.

Whether things work perfectly or problems arise, the whole event has taken no more than a millisecond.

7
Back to Selective Serotonin Reuptake Inhibitors

SSRI Antidepressants
SSRI Antidepressants. Joe Raedle / Getty Images

We started out talking about the meaning of the term "selective serotonin reuptake inhibitor," which is the class of drugs that includes Prozac, Paxil, Zoloft and others. Remember the coffee shop in the illustrations? That's the reuptake transporter, and one theory about depression is that there isn't enough of the neurotransmitter serotonin available in synapses to send messages from one neuron to another. An SSRI's function is to selectively target serotonin coffee shops (the reuptake transporters) until the serotonin messengers have contacted Building 2 (the receiving nerve cell) significantly more times than normally happens in that particular person's brain. Thus, these drugs specifically inhibit the reuptake of serotonin.

And remember that these messages aren't just going from one neuron to another. They're going from millions of nerve cells to millions of others in long chains. If the process is not happening correctly, mood disorders and physical illnesses can be the result.

8
Putting It All Together

The brain is a marvelous thing!
The brain is a marvelous thing - but there are so many things that can go wrong with it. John Lund / Getty Images

Now as you have probably realized, it isn't really this simple. But this illustrated story gives you a basic idea of how neurotransmitters operate and why it is so important that they operate correctly. It's crucial that neither too many nor too few of them are released into the synaptic cleft; that the autoreceptors and enzymes are working properly; and that a myriad of other factors fall into place to contribute to a healthy process.

When they don't, you can get illnesses like Parkinson's disease, which is caused by a dopamine deficiency. You might have schizophrenia, which is thought to be caused in part by an imbalance of dopamine, or epilepsy, apparently caused in part by abnormalities with the neurotransmitters GAGA and glutamate.

The effect of neurotransmitters in bipolar disorder is constantly being studied. As I mentioned at the beginning, serotonin, norepinephrine, and dopamine have all been implicated - the amount of available messengers, the number of messengers of each in relation to the others, the sensitivity of the receptors and reuptake transporters, and the number of enzymes present in the synapses. Anticonvulsants may work as mood stabilizers for bipolar disorder because they make the brain less "excitable," just as they do in epilepsy but in a different setting.

My goal with "GABAs on the Move" has been to provide an easy-to-understand description of basic neurotransmitter functions. Remember the team messengers and their adventures in Brain Complex as you read other articles!

Thanks to Richard Schuergar, Former About Guide to Neuroscience, for his contributions to this article.

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