Nervous System: Neurotransmitters – Biological Bases of Behavior (PSY, BIO)

00:01 Now, let’s move on to the chemical side of this equation.

00:05 So we walked through the action potential, we’re talking about neurons.

00:08 But another really important point is the chemical side of things and that’s mediated by neurotransmitters.

00:15 So they’re known as “chemical messengers” and they’re found endogenously, meaning within us, and they allow for this neurotransmission.

00:22 So we transmit a chemical signal across that synapse from a pre to postsynaptic side and there’s a target there or a receptor and we call it the postsynaptic receptor.

00:32 And these neurotransmitters are stored in vesicles, and we kind of already talked about that and we said that each one typically only has one type of neurotransmitter.

00:41 Now, if the released neurotransmitter depolarizes the postsynaptic membrane, it’s termed an excitatory neurotransmitter.

00:48 An example would be glutamate.

00:51 And the flipside is if you hyperpolarized a postsynaptic cell or go more negative, that becomes inhibitory.

00:58 An example would be GABA.

01:00 So the postsynaptic neuron can integrate several neurotransmitters, and the response that it comes from it before actually initiating a response.

01:08 So, even though the presynaptic will only carry one transmitter, that doesn’t necessarily mean the postsynaptic side is only receiving one neurotransmitter.

01:19 Because in these diagrams and all your textbooks that you’re going to read, you have these overly simplified Mickey Mouse diagrams, which is understandable because we’re trying to understand the basic theory and premise behind this.

01:28 In reality, we have poly innervations or very complex neural networks and we have hundreds, thousands of neurons making different connections to each other.

01:38 So it’s very rare that you have one presynaptic neuron making just a connection with one postsynaptic neuron.

01:44 There’s typically a whole bunch interconnected with one another.

01:48 And in that little synaptic environment, that little small bubble, if we took a look, you would actually have some GABA, some glutamate, maybe some dopamine or whole bunch of different transmitters that are floating around upon stimulation activating these postsynaptic receptors.

02:04 And the end result of what we’re going to see is that bouncing actor, that orchestra of all those different neurotransmitters.

02:10 Okay? So, it’s not necessarily that A gives you B.

02:15 You’re going to have so many different derivatives of A that collectively together will give you the ultimate B which is a postsynaptic response.

02:22 So, as you can see from this figure, we have a lot of various steps.

02:27 And what I’m going to do here is I’m going to fairly, quickly walk through all of the steps in one breath so that you get the scope of the mechanism from beginning to end because you should be quite familiar with the process of synaptic transmission including the action potential and release of neurotransmitters.

02:44 So here we go.

02:45 An action potential is going to travel down the length of the axon and ultimately is going to get down to axon terminal.

02:52 At which point, we’re going to, step one, open voltage-gated calcium channels.

02:59 So same idea, it’s voltage-gated but this time it’s allowing calcium through.

03:03 And that extracellular or outside environment, we have a high concentration of calcium.

03:08 So that calcium is going to want to go in.

03:09 Now once that calcium goes in, it’s actually the on switch or the trigger lighting that bulb or presynaptic side know, “Hey guys, it’s time to release neurotransmitter.” That tells the vesicles to start travelling down and fuse with the presynaptic membrane to that process of exocytosis where it’s going in, binding, and opening its contents to release a transmitter, exocytosis.

03:35 And it does that docking, through docking proteins and this whole process which is sort of beyond this course but it goes in, opens up and releases and now we have electrical going to chemical and releasing that neurotransmitter that are stored in the vesicles into the synaptic cleft.

03:52 It will now flow around in the cleft, travel across to the postsynaptic side where it’ll interact with a postsynaptic receptor causing a conformational change or opening -- simplistically we say we’re opening an iron channel.

04:05 In reality, a neurotransmitter binds to a receptor binding site and causes a conformational change in the receptor which is what causes an opening and that allows ions to come in.

04:17 So what have you, usually it’s sodium rushing in and that allows the signal to continue to move forward and we’ve gone now switching from chemical back to electrical and it is propagated down the length of the postsynaptic neuron.

04:32 Now, we need an off so that neurotransmitter doesn’t float around, and definitely in the synapse, what ends up happening is we get inactivation, and then it happens through a couple of ways.

04:42 First, the postsynaptic receptor will have an off sort of button.

04:48 It will inactivate itself.

04:50 And so, it only stays open for a few moments, turns itself off, and the neurotransmitter that have been bound to the receptor will either be dissociated or it will be broken down through enzymatic activities.

05:02 So enzymes will go that are floating around and break down that transmitter.

05:05 So transmitters have a finite life.

05:07 The other unused transmitter or dissociated transmitter, so the transmitter gets kicked off the binding site that’s floating around in the synapse will also get broken down by enzymes.

05:17 And each transmitter has a very specific enzyme that’s designed to break it down into its components.

05:23 Now, it doesn’t break it down to a point where it’s unusable.

05:25 It actually breaks it down back into the building blocks.

05:28 And the nodes can get retaken back into the presynaptic sides.

05:32 So that’s the third way in which you can end the activity and it’s called “reuptake of transmitter”, and it’s the opposite of exocytosis and it uses endocytosis.

05:42 And that’s it gobbling it back up, repackaging it into the vesicles and those vesicles move back up into their sort of stored site where they’re waiting to go.

05:52 Okay? So, we just walked through electrical to chemical, back to electrical.

05:57 And we also have talked about the different ways you can inactivate the response or turn it off.

06:01 All this is happening, like I said, extremely fast in milliseconds and this neuron is now primed and ready to fire again when needed.

06:12 Okay.

06:13 Now, how do we know something is in your transmitter? So I’ve talked about glutamate.

06:17 I’ve talked about GABA.

06:19 You know, are those the only two? Is there more? Is there a lot more? Well, the answer is there’s actually a growing list of transmitters and they’re always finding new ones and say, “Well, this is actually can be considered a neurotransmitter.” Now, the core list of the ones that are really relevant for you, those haven’t change for, you know, years.

06:34 So you’ve got your glutamate, your GABA, glycine, you know, there are the ones that you’ll hear about a lot.

06:40 Dopamine, these are different transmitters and hormones that are really, really important.

06:44 But there are four main criteria that you need to know that helps us identify something as being a neurotransmitter.

06:51 First of, it has to be synthesized or present in the neuron.

06:55 Okay? So it can’t be coming from somewhere else.

06:56 This is made from within the neuron.

06:58 So if it’s a GABAergic neuron, that neuron needs to have the process in order to synthesize its own transmitter and that’s stored in those vesicles.

07:09 When released, it must produce a response on a target.

07:11 So, it’s kind of not a transmitter if it’s being produced and it’s being released and it’s not doing anything anywhere.

07:17 You need to have a receiver or a target.

07:20 So that would be the postsynaptic target or postsynaptic receptor.

07:24 The same target response must be obtained experimentally.

07:27 So, if I had some postsynaptic receptors that were designed to bind with GABA, if I dumped some GABA on those cells, it needs to activate a response.

07:43 So you wonder, “Well, how do you do that?” This is where we talk about an experimental process called “electrophysiology”.

07:49 Near and dear to my heart, this is what I do a lot of my PhD in, and that’s where you actually record from a specific cell and you record pre and post synoptically and you could administer and apply different drugs, different transmitters and look at the pre versus postsynaptic response depending on what cell you’re recording from.

08:07 So, the idea simply put is if you’re recording from a postsynaptic target, if I apply some GABA, I expect to see a response.

08:16 If I don’t, that means well GABA isn’t really a neurotransmitter.

08:20 Finally, we need to have some form of inactivation.

08:23 So those things that I talk about, the enzymatic breakdown, the reuptake, there needs to be some way to have an off.

08:29 So you need to have an on, you need to have an off, you need to have it being synthesized at the neuron and you need to be able to replicate that response experimentally.

08:37 Okay? So these are four things that need to happen for us to say, “This compound is a neurotransmitter.”