Now, let’s move on to the
chemical side of this equation.
So we walked through the action
potential, we’re talking about neurons.
But another really important
point is the chemical side
of things and that’s mediated
So they’re known as
and they’re found
endogenously, meaning within
us, and they allow for
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.
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.
Now, if the released neurotransmitter
depolarizes the postsynaptic membrane,
it’s termed an excitatory
An example would be glutamate.
And the flipside is if you
hyperpolarized a postsynaptic
cell or go more negative,
that becomes inhibitory.
An example would be GABA.
So the postsynaptic neuron can
integrate several neurotransmitters,
and the response that it comes from it
before actually initiating a response.
So, even though the presynaptic
will only carry one transmitter,
that doesn’t necessarily
mean the postsynaptic
side is only receiving
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.
In reality, we have poly innervations
or very complex neural networks
and we have hundreds,
thousands of neurons making different
connections to each other.
So it’s very rare that you
have one presynaptic neuron
making just a connection with
one postsynaptic neuron.
There’s typically a whole bunch
interconnected with one another.
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
And the end result of what we’re
going to see is that bouncing
actor, that orchestra of all those
So, it’s not necessarily
that A gives you B.
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.
So, as you can see from this figure,
we have a lot of various steps.
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.
So here we go.
So, an action potential is going to travel
down the length of the axon and ultimately
is going to get down to the end of one
of the processes or the dendrites.
At which point, we’re going to, step one,
open voltage-gated calcium channels.
So same idea, it’s voltage-gated but
this time it’s allowing calcium through.
And that extracellular
or outside environment,
we have a high
concentration of calcium.
So that calcium is going
to want to go in.
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.
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.
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.
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.
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.
Now, we need an off so that
float around, and
definitely in the synapse,
what ends up happening
is we get inactivation,
and then it happens
through a couple of ways.
First, the postsynaptic receptor
will have an off sort of button.
It will inactivate itself.
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.
So enzymes will go that are floating
around and break down that transmitter.
have a finite life.
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.
And each transmitter has
a very specific enzyme
that’s designed to break it
down into its components.
Now, it doesn’t break it down
to a point where it’s unusable.
It actually breaks it down
back into the building blocks.
And the nodes can get retaken
back into the presynaptic sides.
So that’s the third way in
which you can end the activity
and it’s called “reuptake
and it’s the opposite of exocytosis
and it uses endocytosis.
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.
So, we just walked through electrical
to chemical, back to electrical.
And we also have talked
about the different ways
you can inactivate the
response or turn it off.
All this is happening, like
I said, extremely fast
in milliseconds and this neuron is now
primed and ready to fire again when needed.
Now, how do we know something
is in your transmitter?
So I’ve talked about glutamate.
I’ve talked about GABA.
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.
So you’ve got your glutamate,
your GABA, glycine,
you know, there are the ones
that you’ll hear about a lot.
Dopamine, these are
different transmitters and
hormones that are really,
But there are four main criteria
that you need to know that
helps us identify something
as being a neurotransmitter.
First of, it has to be synthesized
or present in the neuron.
Okay? So it can’t be coming
from somewhere else.
This is made from
within the neuron.
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.
When released, it must produce
a response on a target.
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.
You need to have a
receiver or a target.
So that would be the postsynaptic
target or postsynaptic receptor.
The same target response must
be obtained experimentally.
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.
So you wonder, “Well,
how do you do that?”
This is where we talk about an experimental
process called “electrophysiology”.
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.
the idea simply put is if you’re
recording from a postsynaptic target,
if I apply some GABA, I
expect to see a response.
If I don’t, that means well GABA
isn’t really a neurotransmitter.
Finally, we need to have
some form of inactivation.
So those things that I talk
about, the enzymatic breakdown,
the reuptake, there needs to
be some way to have an off.
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.
So these are four things
that need to happen for
us to say, “This compound
is a neurotransmitter.”