Neurotransmitters are involved in the dialogue between neurons, nerve cells, and neurotransmitters tend to mediate local communication. Just imagine two people talking to one another at a concert, that communication between them is analogous to the communication carried out by neurotransmitters, whereas neuromodulators influence the communication of many neurons.
Neurotransmitters are dumped out of the terminals of one cell and they diffuse across the space between the two cells, which is kind of a liquidy space. And they hit some receptors on the postsynaptic cell and they have some impact. Sometimes that's not through a regular synapse. Sometimes it's through a neuromodulator, like you often talk about on your podcast that are sort of oozing dopamine, exactly, oozing into the space between the cells.
of SSRIs and neuroleptics or drugs that tap into the so-called dopamine system or the glutamate system. These are other neurotransmitters and neuromodulators that impact different circuits in the brain. And just to really remind you what neurotransmitters and neuromodulators do, because this is important to contextualize all this, neurotransmitters are typically involved in the rapid communication between neurons.
The neuromodulators, by contrast, so not neurotransmitters, but neuromodulators, like dopamine, serotonin, epinephrine, and acetylcholine, and others, operate a little bit differently. They intend to act a little bit more broadly. They can act within the synapse, but they can also change the general patterns of activity in the brain, making certain circuits more likely to be active and other circuits less likely to be active.
They tend to impact many more neurons all at once. And they go by names like dopamine, serotonin, acetylcholine, epinephrine, and so forth. Sometimes people refer to those as neurotransmitters. Technically they are neuromodulators. I'll refer to them almost always as neuromodulators. The neuropod cells signal by way of a particular branch of the vagus through the nodos ganglion that we talked about before, and through a number of different stations in the brainstem eventually caused the release of the neuromodulator dopamine.
So these are brain chemicals. They're different from dopamine and serotonin in that they're not small organic molecules. They're actually short pieces of protein that are directly encoded by genes that are active in specific neurons and not in others. And when those neurons are active, those neuropeptides are released together with classical transmitters like glutamate, whatever.
Neuromodulators are different than neurotransmitters in the sense that neuromodulators modulate or change the activity of brain areas and neural circuits. You can think of them as microphones that are held between particular sets of connections in the brain that make those connections in the brain more likely to be active relative to others.
Good examples of neuromodulators are dopamine, serotonin, acetylcholine, norepinephrine. These tend to work on different systems in the brain and body, but they tend to be activated more or less in parallel. You can have dopamine released in your brain and also norepinephrine. You can have serotonin released in your brain and also acetylcholine.
To remind you neuromodulators are these chemicals that act rather slowly, but their main role is to bias particular brain circuits to be active and other brain circuits to not be active. These are like the music playlist. So think of neuromodulators, and these come in the names of acetylcholine, norepinephrine, serotonin, and dopamine.
They're called neuromodulators. And those neuromodulators have names that probably you've heard of before, things like dopamine and serotonin and acetylcholine, epinephrine. Neuromodulators are really interesting because they bias which neurons are likely to be active and which ones are likely to be inactive.
Okay, they make them louder, so to speak. There are many neuromodulators, but the ones that are important for sake of today's discussion are the classic ones, dopamine, acetylcholine, norepinephrine, and serotonin. Let's focus on serotonin. Serotonin is a neuromodulator that tends to increase the activity of certain neural circuits, including within the hypothalamus, but also within the body, that trigger a sense of satiety of having enough, enough food, enough warmth, enough social connection, enough of any motivated goal or drive
Is it known whether or not any of those molecules are small enough to cross the blood brain barrier? Because the hypothesis and the current thinking is that neurotransmitters manufactured in the gut and signaling along the gut brain axis, literally neurons talking back and forth electrically from brain to gut and gut to brain is what regulates things like mood or at least in animal models.
All of that can be controlled to a considerable extent by leveraging these so-called neuromodulators. What are neuromodulators? Neuromodulators are particular chemicals that make it likely that certain neural circuits will be active and not others. And the four neuromodulators that we're going to talk about today that are of the utmost importance for your goals are dopamine, epinephrine, also called adrenaline, serotonin, and acetylcholine.
Spikes of action potentials, meaning those neural signals, cause the release of chemicals in the brain like dopamine. So it's chemical transmission. Similarly, hormones, even though they act more slowly, hormones like neuropeptide Y, like CCK, like ghrelin, they are signaling chemically. They're moving through the body.
Those neurotransmitters are vomited out. They're not actually vomiting, but they're spit out into the so-called synaptic cleft, often called the synapse. The synapse is just a little gap between neurons. And when they are released into the synapse, they don't just stay there. They actually park or bind to receptors on what's called the postsynaptic neuron.
And the immediate question should be, well, why? Well, the answer is that when we pay careful attention, there are two neurochemicals, neuromodulators as they're called, that are released from multiple sites in our brain that highlight the neural circuits that stand a chance of changing. Now it's not necessarily the case that they're going to change, but it's the first gate that has to open in order for change to occur.
A simple way to think about neuromodulators is they are sort of like playlists that you would have on any kind of device where you're going to play particular categories of music. So for instance, dopamine, which is often discussed as the molecule of reward or joy, is involved in reward. And it does tend to create a sort of upbeat mood when released in appropriate amounts in the brain.
And the two most common neurotransmitters for that are the neurotransmitter glutamate, which we say is excitatory, meaning when it's released into the synapse, it causes the next neuron to be more active or active. And GABA, which is a neurotransmitter that is inhibitory, meaning when it's released into the synapse, typically, not always, but typically, that GABA is going to encourage the next neuron to be less electrically active or even silence its activity.
And I acknowledge that there are many neuromodulators, there are indeed many neurotransmitters, glutamine, glycine, GABA, et cetera, but today we focused on the main four, meaning the most potent and most widespread neuromodulators in the brain and body that give you access to particular brain states and body states of the sort that most people desire.
Let me explain what these are. Serotonin again is a neuromodulator. Neuromodulators are a little bit like playlists in the brain. They tend to amplify or bias the likelihood that certain brain circuits and body circuits are going to be activated and that others will not. Serotonin generally, and I realize I'm speaking very generally here, but it generally gives us feelings of wellbeing at very high levels.
They make certain brain areas more likely to be active and other brain areas less likely to be active. These neuromodulators have names like dopamine, serotonin, acetylcholine, epinephrine, and so on. The main neuromodulators associated with gratitude and pro-social behaviors tends to be serotonin. Serotonin is released from a very small collection of neurons in the brainstem called the raphe, R-A-P-H-E, the raphe nucleus, and a few other places in the brain.
More typically, it gets assistance from some of the other neuromodulators. Now, that might seem like it complicates the picture, but it actually makes the picture far simpler, because what we can say for sure is that the fast actions of dopamine, or the fast actions of epinephrine, serotonin, or acetylcholine, are actions that occur on the order of seconds or minutes or up to about an hour or so, whereas the slower actions of those neuromodulators tend to occur on the order of hours, days, or even weeks.
It's released out over a bunch of neurons. In both cases, it's released from these things we call synaptic vesicles, literally little bubbles, tiny, tiny little bubbles that contain dopamine. They get vomited out into the area or into the synapse. Well, those vesicles get depleted. For the synaptic physiologists out there, we call this the readily releasable pool of dopamine.
So these neuromodulators can exist in normal levels, low levels, high levels. And that actually gives us a window into a very important aspect of neuroscience history that all of us are impacted by today, which is the discovery of antidepressants and so-called antipsychotics. In the 1950s, 60s, and 70s, it was discovered that there are compounds, chemicals, that can increase or decrease serotonin, that can increase or decrease dopamine.
So much so that today we're going to talk about, for instance, the presence of neurons, nerve cells, that reside in your gut that communicate to specific locations in the brain and cause the release of specific neurochemicals, such as the neurochemical dopamine or serotonin, that can motivate you to seek more of a particular food or type of interaction or behavior, or to avoid particular foods, interactions, and behaviors.
Well, they don't literally vomit, but they release little packets of so-called transmitter chemical into that space we call a synapse. It travels across the synapse, it attaches to the cell on the other side, the other neuron, and then depending on what that chemical is, it either makes that next neuron more electrically active or less electrically active, so-called excitation.
That's dopamine, epinephrine, serotonin, and acetylcholine. Today I'm going to teach you how each of those different categories of neuromodulators work and the things that you can do to control those neuromodulators, that is increase them or decrease them through behavioral tools and supplementation in ways that allow you to access the brain and body states that you want at the times that you want.
And that's because of the relationship to choline in the biosynthesis pathway for acetylcholine. Acetylcholine is a neuromodulator, not a neurotransmitter, but a neuromodulator in the brain. A neuromodulator is a chemical that modulates the function of many brain circuits and also circuits within the body.
Norepinephrine is a neuromodulator that tends to amplify the brain circuits associated with alertness and the desire to move. Serotonin is the neuromodulator that's released and tends to amplify the circuits in the brain and body that are associated with bliss and the desire to remain still. And dopamine is the neuromodulator that's released and is associated with amplification of the neural circuits in the brain and body associated with pursuing goals and pleasure and reward, okay? So in slow wave sleep, something really interesting happens.
Now, the other thing to understand about dopamine is that the way that dopamine is released in the brain and body can differ, meaning it can be very local or it can be more broad. Now, most of you have probably heard of synapses. Synapses are the little spaces between neurons and basically neurons, nerve cells, communicate with one another by making each other electrically active or by making each other less electrically active.