That Neuroscience Guy - The Neuroscience of Neurotransmitters

Episode Date: February 28, 2025

Neurotransmitters are essential cellular components for neural function - and they're common targets for treatment of several psychiatric and neurological disorders. In today's episode of That Neuroscience Guy, we review all of the important neurotransmitters that underlie neural function.

Hi, my name is Olav Krogolson and I'm a neuroscientist at the University of Victoria. And in my spare time, I'm that neuroscience guy. Welcome to the podcast. So over the course of the podcast, we've talked a lot about neurotransmitters and there's a lot of buzz out there about neurotransmitters. Like we talk about addiction to social media and we're talking about dopamine, we're talking about depression

and we might be getting into serotonin. So what I want to do today is do the neuroscience of neurotransmitters and just give you sort of like an A to Z if you will of the major neurotransmitters and just give you sort of like an A to Z, if you will, of the major neurotransmitters and what they do. So this episode's a bit of a reference, if you will, something you can look back to, to, well, hey, what's this neurotransmitter all about again?

So on today's episode, the neuroscience of neurotransmitters. I guess the best place to start is what is a neurotransmitter? What does it actually do in your brain? Well, the way they work is pretty straightforward. Imagine that two neurons are connected, okay? So neuron A, which we'll call the presynaptic neuron, is connected to neuron B, which is the postsynaptic neuron. Now, where neurotransmitters come in is when a neuron fires, it's an electrical signal. We call it an action potential.

We've talked about it. It goes down the axon, and then it reaches the axon terminal, or the bouton at the end of the axon. And when that electrical signal gets there through a biochemical reaction or electrochemical reaction more correctly, neurotransmitters released by the neuron. All right, and it's released at the synapse. And when it binds to a postsynaptic neuron, depending on what that neuron does, what it targets, and what the neurotransmitter is,

that depends on the result. So let's start with glutamate, which is the major or the main excitatory neurotransmitter in the CNS. So most of the neurons in the brain are interneurons, that's neurons connected to other neurons, and when they fire their whole purpose is just to fire another neuron. That's how information is passed. So when an action potential occurs in one of these neurons, when that action potential reaches the synapse glutamate is released and glutamate drifts across the

synapse and when it binds it excites and glutamate drifts across the synapse, and when it binds, it excites the postsynaptic neuron, making it more likely to fire. So let's just say you want to build a relationship between a face and a name. Now obviously it'd be way more neurons than two, but let's simplify it to one neuron that represents the face and one neuron that represents the name.

So when you see the face, you want to excite the neuron that represents the face and one neuron that represents the name. So when you see the face, you want to excite the neuron that represents the name, and that's the link between the two of them. So that's an excitatory connection. So when the face neuron fires, glutamate is released, which excites the name neuron, and then it fires, and then you've got that association between the two of them.

Now, we don't just want excitatory connections. We want inhibitory connections. Sometimes you want a neuron not to fire. So for instance, if you see a face and that face goes with the name Bob, you don't want the name Jill to fire. So you might want to inhibit that connection. Another example of inhibition is muscle tremor. If you get muscle tremor due to Parkinson's, for instance, one of

the reasons that's happening is you're not inhibiting some neurons, so you've got motor units firing that shouldn't be firing, and that results in tremor. So when neuron A fires, it releases a neurotransmitter that inhibits or reduces the chance that the post synaptic neurons gonna fire. And the two primary neurotransmitters for that are GABA and glycine. Alright, GABA plays an inhibitory role in the brain and glycine plays an inhibitory role in the spinal cord and that's where you see these neurotransmitters being released. So glutamate is the main excitatory neurotransmitter and GABA and glycine are the main inhibitory

neurotransmitters, GABA brain glycine spinal cord. Now, there's a whole bunch of other neurotransmitters that do other things. Glutamate, GABA and glycine we typically refer to as amino acids, But now if we talk about other neurotransmitters, there's a whole bunch of them out there. Let's start with acetylcholine just to go through these in no particular order. Basically acetylcholine plays a role in the parasympathetic response, so the

responses of the parasympathetic response. So the response is the parasympathetic nervous system. And if you remember the parasympathetic and the sympathetic nervous systems, you know, they're excitatory and inhibitory. All right, one makes the heart go faster, one slows the heart down, and so on and so forth. So acetylcholine is the main neurotransmitter for the parasympathetic nervous system.

And it also plays a role with maintaining and firing skeletal muscle and also memory. Epinephrine is the main sympathetic neurotransmitter. So for the sympathetic nervous system, you see epinephrine coming in. So acetylcholine for the parasympathetic nervous system, epinephrine for the sympathetic nervous system. Now, like I said, there's a whole bunch more. There's something called norepinephrine. So what does norepinephrine do?

Well, it's tied to the response of the sympathetic nervous system, but at a higher level, it impacts our arousal levels. So the release of norepinephrine increases arousal levels. So the release of norepinephrine increases arousal levels. So in other words, your fight or flight response at a low level. It also helps with attention. Norepinephrine is released when you need to focus your attention and it plays a role in mood. Norepinephrine is being tied to a bunch of different moods, but generally, the difference between happiness and sadness isn't just norepinephrine, but it plays a role in our nervous system expressing those emotions.

Another one with norepinephrine that's kind of interesting is decision-making. If you need to make decisions, norepinephrine is released to actually enhance your decision-making system. My own lab's done some research there and it's kind of cool. You basically are releasing norepinephrine when you're in decision situations that require you to do a lot of thinking or cognitive effort and if you're just doing gut hunch decisions you're just responding

instinctively you don't need that release of norepinephrine and basically what it's doing it when it's doing when it's released is it's just optimizing neural firing. Dopamine, we've talked about dopamine a lot. You know from previous podcasts, it's tied to reward and reinforcement. We've talked about dopamine in terms of addiction to social media, but also addiction to certain drugs.

When you do cocaine, for instance, it causes a release of dopamine and it's what causes the addiction to cocaine. It plays a role in motivation, dopamine is associated with that, and does play a role in motor control as well. Dopamine plays a role in your ability to control movements, especially in the in the basal ganglia region. And it's important to note this now that dopamine is a sort of a generic name.

There's actually different types of dopamine, if you will, and these different types of dopamine bind at different receptors, and that causes these different responses. It also has to do where in the brain dopamine is hitting. If it hits in a part of the brain associated with reward learning, that's the role it's playing. If it's released in motor regions, then it's helping maintain the motor system. Serotonin is another one that's out there. Serotonin, big in depression, a lot

of antidepressants target serotonin. There are actually antidepressants that target the dopamine system as well. It depends on what's driving the depression. But serotonin also plays a role in digestion, your sleep cycle, anxiety, mood, appetite, social behavior. So serotonin is a big neurotransmitter in terms of our interactions with the world, if will and like I said depressions a classic, but like I said Anxiety is another one people with anxiety typically have higher serotonin levels than would be appropriate Another one that's out there which we've heard about is histamine Wakefulness is the big one. All right So histamine plays a role in your ability to stay awake.

Low histamine levels, not good for being awake. High histamine levels, better for being awake. It also plays a role in the body in terms of inflammatory responses, your responses to injury, if you will. There's a couple other ones out there. Endorphins are a big category of things. Euphoria is a big one, like happiness, it's out there. Endorphins are a big category of things. Euphoria is a big one like happiness.

It's out there. So endorphins are released and guess what? There's a couple of different types of them. But when they're released, it's that happiness or euphoric or feeling and that's it. There's an interesting one out there that goes by the name of substance P. Substance P is, I'd call it a newer neurotransmitter. It's been tied to pain transmission and the pain response in the brain. And another one out there is nitric oxide. It's a form of neurotransmitter. All right, it comes in a very specific form in that role. It's actually a gaseous molecule, but it helps with muscle dilation, the way that muscles basically do their thing.

It helps smooth it out. It also plays a key role in your immune response. So those are the major neurotransmitters in the brain. Like I said, glutamate by far is the biggest neurotransmitter in the brain, or at least that's what you have the most of, but followed closely by GABA and glycine, your inhibitory neurotransmitter in the brain or at least you have the that's what you have the most of but followed closely by GABA and glycine your inhibitory neurotransmitters. All right then we went through a list of a whole

bunch of other neurotransmitters acetylcholine, epinephrine, norepinephrine, dopamine, serotonin, histamine, endorphins, substance P and nitric oxide. The key thing in a general sense is just to reiterate how they're used. A neuron fires, it releases neurotransmitter at the synapse. That neurotransmitter crosses the synapse and then when it binds on the post-synaptic neuron, it generates an electrical signal or it generates a response.

And depending on the type of neuron and the neurotransmitter, depends on the type of response that you get. Now, I'll give you one last example, one that's near and dear to my heart because it's tied to reinforcement learning, which is where I started my graduate studies. Let's say you're repeating a motor skill,

you're learning tennis, and you've got neuron A connected to neuron B in the motor system, and you want to link these two neurons. If these two neurons are linked, you've got a better motor response, okay? Your tennis serve is better, or your tennis forearm is better. Through heavy and learning or repetition, that connection will get strengthened. And if you remember our episode on neuroplasticity, what that means is more glutamate would be released, or there might be more postsynaptic receptors

to receive glutamate. So literally the Hebbian learning process, we talked about long-term potentiation with that as well, you're releasing more glutamate or you have more glutamate receptors. So you're increasing the excitatory response to strengthen that connection. But if you look at reinforcement learning,

you're also processing feedback, whether you did it right or wrong. And if you did it right, there's also a release of dopamine at the synapse. Now the neurotransmitters don't get bind together, don't get mixed together. Dopamine, the dopamine neuron actually attaches to the posts synaptic neuron

and the release of dopamine also plays a role in increasing the number of receptor sites that are available for glutamate. So for this learning situation of learning this motor skill, you've got more glutamate being released through repetition, you've got dopamine being released through feedback, positive feedback saying you've done it right, and together those neurotransmitters work to strengthen that connection. And that's true of all the neurotransmitters I've mentioned. Released at the synapse, when they bind they do the different things that I've outlined. Alright, that's a bit on the neuroscience of neurotransmitters. Hopefully you found that interesting. Don't forget Patreon to those of you that support us with donations every week or every month.

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