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.
