Professor Dave again, let’s talk about neurons and synapses.
When we studied nervous tissue in the anatomy and physiology course, we discussed the mechanism
by which neurons conduct and transmit electrochemical signals throughout the body.
These signals relay information about a person’s surroundings from sensory organs to the brain,
and then from the brain back to the rest of the body to tell it how to respond.
That tutorial was a basic introduction to this topic, and it is one which must be viewed
first before moving on with this playlist.
But if you’re up to speed with the basics, let’s go through the whole thing again in
more detail so that we are prepared to understand all of the things we will discuss for the
remainder of this series.
In learning about how neurons work, the most important concept to understand will be the
notion of membrane potential.
This is a kind of electric potential, a concept we discussed from the standpoint of physics
in the classical physics series.
To put it as simply as possible, electric potential describes the amount of work that
must be done to separate oppositely charged particles that are attracted to one another,
just the way that gravitational potential describes the amount of work that must be
done to move a massive object away from the source of a gravitational field.
It can also describe the work that can be produced by the spontaneous motion of charged
particles along their concentration gradients, kind of like water flowing downstream and
pushing a waterwheel.
In a neuron, such a potential exists by virtue of the distribution of electrical charge on
either side of the cell membrane.
There are many positively charged sodium and potassium ions in both the cytoplasm and the
extracellular fluid, and for a resting neuron, there are more sodium ions outside than inside,
and more potassium ions inside than outside.
These ions will tend to diffuse along their concentration gradients, which means they
will have a tendency to disperse as much as possible until their concentrations are the
same everywhere, as entropy demands.
But the cell membrane, with its nonpolar region, makes it very difficult for the ions to do
so, leaving only surface proteins called ion channels as passageways for travel.
This results in some potential energy for the system, with ions that have the potential
to move, just the way an elevated object has the potential to fall down to the ground.
This resting potential is measured as being about negative 70 millivolts, and in this
state the neuron is said to be polarized.
Now the electric potential can deviate from this resting potential, due to the fact that
the membrane permeability of sodium, potassium, calcium, and chloride ions, or their ability
to pass through the membrane, can change depending on the status of certain membrane proteins.
When looking at a resting neuron, the permeability of sodium is very low, because sodium ion
channels are typically closed, while potassium has a higher permeability because potassium
ion channels are open, though the ions are largely held in place by the negative resting
potential, given that negative charge builds up on the inner surface of the membrane as
potassium ions leave the cell, until they no longer have the tendency to do so.
This results in significant pressure on sodium ions to enter the neuron, due to both the
pressure of random motion to follow the concentration gradient, as well as the electrostatic pressure
from the negative charge build-up, which attracts the positively charged sodium ions.
But as we said, the status of these ion channels will change at specific times, and this is
mediated by signaling molecules called neurotransmitters.
Later in the series we will do a comprehensive survey of all the different neurotransmitters,
but for now let us just consider them in a very general sense.
When a neurotransmitter arrives at a neuron and binds to an ionotropic receptor in the
cell membrane, this will cause a conformational change in the receptor such that ions can
pass through.
This will have an effect on the membrane potential.
The result could be depolarization, which makes the resting potential less negative,
or hyperpolarization, which makes the resting potential more negative.
In either case the change is small, just a couple millivolts.
Depolarization excites the neuron, making it more likely to fire, while hyperpolarization
inhibits the neuron, making it less likely to fire.
These are both forms of graded responses, which means that the magnitude of the change
in potential is proportional to the intensity of the signal, or the amount of neurotransmitters
that bind.
As ions traverse the membrane and the voltage changes, this will cause nearby voltage-gated
ion channels to open, which allows for the diffusion of more ions.
If the sum of this activity is sufficient to depolarize the membrane beyond its threshold
of excitation, which is usually around negative 55 millivolts, an action potential will be
generated.
This involves the propagation of this electrochemical activity all the way along an entire axon.
All the voltage-gated sodium channels in the membrane along the axon open up sequentially,
and sodium ions rush in.
This triggers the opening of voltage-gated potassium channels, and potassium ions rush out.
At the terminal end of the axon, this activity triggers the release of more neurotransmitters,
which travel across the synaptic space to interact with another neuron and continue
the signal.
In this way, communication occurs through a series of synapses.
The pre-synaptic neuron releases neurotransmitters to activate receptors on the post-synaptic
neuron, triggering an action potential that propagates the signal to the next neuron,
and the next, moving throughout the body in this fashion.
This may seem like an incredibly elaborate process, far too elaborate to account for
our rapid reflexes, but don’t forget that chemistry happens on a time scale that is
imperceptible to humans.
The molecular world operates on the order of picoseconds, which are trillionths of a
second, meaning that billions of chemical events can happen quickly enough on this tiny
scale to produce a macroscopic effect, such as the motion of your body parts, which we
merely perceive as being instantaneous.
Now let’s talk a bit more about this action potential.
We will commonly see diagrams like this, which show how the membrane potential changes over time.
The horizontal portions represent the resting potential, which as we said, will be around
negative 70 millivolts.
When neurotransmitters are received by a neuron, if the effect is a depolarization, which as
we said results in excitation, this is called an excitatory postsynaptic potential, or EPSP.
That’s this little hill we can see here.
If the effect is hyperpolarization, we know this results in inhibition, and that’s called
an inhibitory postsynaptic potential, or IPSP.
That’s this little dip here.
If depolarization occurs and it is of sufficient magnitude so as to surpass the threshold of
excitation, an action potential will be produced, and that’s what this is here.
The tiny little bump is the EPSP, and then we see a sharp and pronounced spike, with
the membrane potential jumping up to about positive 50 millivolts.
This complete reversal of the membrane potential is due to ions diffusing across the membrane
all along the entire axon, and it is very sharp because it is not a graded potential.
It does not rely on the intensity of the stimulus.
If the threshold is reached, the action potential is produced, and if it is not reached, it
won’t be produced.
This is what we call an all-or-none response, kind of like squeezing a trigger until a gun fires.
Once squeezed sufficiently, the gun will fire, and squeezing more will not produce any additional effect.
In addition, if a neuron receives multiple signals roughly simultaneously, these will
be integrated.
So multiple IPSPs produce a single IPSP of greater magnitude.
One EPSP and IPSP will cancel each other out.
Multiple EPSPs produce a single EPSP of greater magnitude, and this last scenario is how the
threshold of excitation is reached to produce the action potential.
As we said, this whole process begins with ligand-gated channels that are activated by
neurotransmitters, thus producing a graded potential, causing voltage-gated channels
to open, and if enough ions diffuse so as to surpass the threshold, the action potential
is generated.
What is the time frame associated with these events?
Well the rising phase begins when the sodium channels open, shortly after which the potassium
channels open, and the membrane potential rises rapidly for about a half millisecond.
At this point, the sodium channels close, while further efflux of potassium ions causes
the potential to drop again.
This phase is called repolarization, also lasting about a half a millisecond.
Then the potassium channels gradually close, which allows more potassium ions to leave
the cell than are necessary, resulting in a lengthier phase called hyperpolarization.
This takes about two full milliseconds or a hair more.
After all of this activity, a variety of membrane proteins will allow ion concentrations to
reset, such as sodium-potassium pumps, which utilize active transport, spending ATP and
shuttling both sodium and potassium ions back to their respective sides of the membrane,
thus restoring the concentration gradient that provides the resting potential.
Once re-established, there will be a refractory period of around one to two milliseconds where
the neuron is incapable of firing again, which we call the absolute refractory period, after
which there is a brief relative refractory period, where it is possible for the neuron
to fire again, but only through excessive stimulation.
Then the neuron returns to its normal resting state.
This serves an important biological function.
It ensures that signals travel in one specific direction along an axon, and it prevents the
neuron from firing repeatedly due to continuous low-level stimulation, firing a maximum of
about one thousand times per second.
In general, the action potential travels very fast, around 100 meters per second or more,
and the precise speed will depend on the type of neuron.
Myelinated fibers offer some insulation and therefore exhibit an increased rate of conduction,
resulting in something called saltatory conduction.
This is because the signal will travel fastest in these areas, with sodium channels concentrated
at the nodes of Ranvier.
That’s why these neurons make up the peripheral nervous system, where reaction time can be
a matter of life and death.
Nonmyelinated fibers propagate the action potential more slowly, so these are found
in certain internal organs where speed can be sacrificed without detriment.
We should point out that this model we have been discussing most accurately describes
conduction in a motor neuron of the peripheral nervous system, and is thus a simplified model.
In mammalian brains like ours, there are many different types of neurons.
Some have very short axons, or none at all, which means no action potential, and conduction
is passive and decremental, meaning it is initiated and then simply weakens as it moves
along the membrane.
Some fire continually even with no stimulus.
Their action potentials can vary in frequency, amplitude, and duration.
Some show action potentials along dendrites, so this activity is not strictly limited to
an axon.
Cerebral neurons are much more varied and complex than motor neurons, so we must keep
that in mind when integrating the model we have discussed with brain activity, and we
will discuss this in greater detail as we move through the series.
Before moving forward, let’s briefly zoom in on the synapse.
Here we can see one of the many axon terminals of a pre-synaptic neuron, the post-synaptic
neuron, and the synaptic space, or synaptic cleft between them, which is very narrow.
The type of synapse depends on the location where it meets the post-synaptic neuron.
Axodendritic synapses connect at a dendrite, while axosomatic synapses connect at the cell
body of a neuron.
These are the two most common situations, though there are others, like axoaxonal when
connecting at the axon, or even dendrodendritic, when connecting from dendrite to dendrite.
In any case, neurotransmitters are produced in the cytoplasm at each of the thousands
of axon terminals, and then packaged into vesicles, which are stored near the membrane.
When the action potential reaches these terminals, voltage-gated calcium ion channels will open,
and calcium ions will enter.
These act as messengers, interacting with a protein which then causes the vesicles to
fuse with the membrane, thus allowing for neurotransmitter release via exocytosis.
These signaling molecules are released into the synaptic cleft, where they can diffuse
until reaching the receptors on the post-synaptic neuron.
The neurotransmitters act as ligands for these receptors, and each specific neurotransmitter
will be able to bind to a certain type of receptor, thus different neurotransmitters
can relay different types of messages throughout the brain.
As we mentioned, ligand binding will cause the ion channel associated with an ionotropic
receptor to open due to a conformational change, and ions diffuse, generating graded potentials
and eventually an action potential.
Once an action potential is generated, the neurotransmitters must leave the receptors
so as to allow for another signal to be transmitted.
Sometimes they will undergo reuptake by the pre-synaptic neuron, while other times they
will be degraded in the synaptic cleft by enzymes.
Either way, once this is complete, everything is ready to begin again with a new impulse.
Now that we have a better understanding of how these signals propagate through the nervous
system, let’s continue on with our study of the brain.