SYNAPSES: https://www.youtube.com/watch?

v=k5RafiYXieo

A synapse is a region where two neurons come close enough to one another that they’re able to
communicate. This capacity for neural communication is one of the key things that gives the nervous
system its diverse and impressive capabilities.

It’s thought that most neurons have thousands of synapses, and although estimates for the total number
of synapses in the human brain vary, they’re always extremely high—ranging from hundreds of trillions
to over two quadrillion.

Because each of these synapses represents an area where neurons can talk to one another, synapses are
the way that neurons in the brain form circuits that enable them to work together to accomplish tasks
ranging from simple movement to complex cognition.

Most neurons rely on both electrical and chemical signaling to spread messages throughout the brain.

Electrical signals are mostly used to send messages from one end of a neuron to another; these are
called action potentials.

But once that action potential has reached the end of a neuron and regions known as axon terminals or
synaptic boutons, it usually needs to prompt the release of a chemical signal to pass the message to the
next neuron. Those chemical signals are called neurotransmitters, and they’re released at chemical
synapses.

Most of the time a synapse is formed between the axon terminals of one neuron and the dendrites of
another. These are called axodendritic synapses.

So that’s what we have right here, is an axodendritic synapse, and this is a close-up of an axodendritic
synapse.
We’ll use an axodendritic synapse as an example because they’re the most common type of synapse, but
it’s important to note that synapses can actually form between any two components of a neuron, such as
between the axon terminals and dendrites, axon terminals and cell bodies, axon terminals and axons, or
even dendrites and dendrites.

So at an axodendritic synapse, the axon terminals of one neuron are situated very close to the dendrites
of another. They don’t actually come into contact with one another, though. There’s a microscopic space
separating them; that space is known as the synaptic cleft.

A synaptic cleft is a very small space; it’s usually somewhere around 20-40 nanometers wide. A
nanometer is a billionth of a meter, so this size is not something that we can easily conceptualize. But a
human hair is about 80,000-100,000 nanometers wide and the head of a pin is about a million
nanometers wide. So we’re talking about a very small space.

The neuron that will be sending a signal across the synaptic cleft is called the presynaptic neuron.

The neuron that will be receiving the signal is called the postsynaptic neuron.

So what happens is we have this electrical signal, this action potential, that’s traveling down the axon of
the presynaptic neuron, and when it reaches the axon terminal it causes changes in the electrical
properties of the interior of the cell, and that prompts a series of events that leads to the mobilization of
structures called synaptic vesicles.

Synaptic vesicles are tiny sac-like organelles that contain neurotransmitter molecules. There are usually
around 100-200 vesicles in each axon terminal of a presynaptic neuron, and each vesicle typically
contains thousands of neurotransmitter molecules. These synaptic vesicles attach and fuse with the cell
membrane of the presynaptic neuron, and by doing so they release their neurotransmitters into the
synaptic cleft in a process called exocytosis.

Once the neurotransmitter molecules enter the synaptic cleft, they diffuse across the cleft and interact
with proteins called receptors. So these receptors are typically found embedded in the membrane of the
postsynaptic neuron, and the neurotransmitter molecules can bind, or attach, to these receptors, and
when they do, they prompt changes in the postsynaptic neuron that might make that neuron more or
less likely to fire an action potential of its own.

After those neurotransmitters have interacted with receptors on the postsynaptic neuron, their job of
transmitting the message from one neuron to the next is done.

But once that job is complete, a next important step is to remove the neurotransmitter molecules from
the synaptic cleft. and this continued interaction could impair the ability of the synapse to remain
functional.

For example, when some receptors are overstimulated, they can stop working for a period of time. This
would prevent further signals from getting through, and disrupt the functionality of the synapse, which
in many cases needs to be able to go through another round of neurotransmitter release and binding
rapidly after the last round.

So, a critical aspect of synaptic transmission is the removal of neurotransmitters from the synaptic cleft.
Some of this happens through simple diffusion. In other words, some neurotransmitter molecules will
just float out of the synaptic cleft. This mechanism, however, only accounts for a small percentage of
neurotransmitter molecules, so it isn’t enough to terminate synaptic transmission on its own.

Another method of removing neurotransmitters from the synaptic cleft is through the use of enzymes.

So enzymes can inactivate and break down neurotransmitters, a process known as enzymatic
degradation. The neurotransmitter acetylcholine, for example, is broken down by an enzyme called
acetylcholinesterase. This enzyme breaks acetylcholine down into its constituent parts, choline and
acetate, and these products can be taken back up into the presynaptic neuron and used to make more
acetylcholine.

A more common method of removing neurotransmitters from the synaptic cleft, however, is a process
called reuptake. In reuptake, a protein called a transport protein, which typically sits embedded in the
membrane of the presynaptic neuron, that protein takes the excess neurotransmitter back up into the
neuron that released it, that’s why it’s called reuptake. And in many cases, these neurotransmitters can
be recycled and repackaged into vesicles to be released again.

The process of reuptake is important to understand because it’s a target for a number of drugs. Selective
serotonin reuptake inhibitors, for example, or SSRIs, are drugs that inhibit the reuptake of serotonin, and
they’re our most common treatment for depression. By inhibiting the reuptake of serotonin, this makes
serotonin more likely to accumulate in the synaptic cleft, thereby increasing serotonin levels. And for
reasons that we don’t fully understand, this increase in serotonin levels seems to be associated with an
improvement of depressive symptoms in some people.

So I’ve described the primary activities at a chemical synapse, and while most communication between
neurons in the adult nervous system involves neurotransmitters and chemical synapses, there are some
synapses that use electrical signaling as their primary mode of communication. And while these are
relatively rare in the adult human nervous system, they’re much more common in the embryonic human
nervous system and they’re common in invertebrate and non-mammalian nervous systems.

At an electrical synapse, neurons communicate at a specialized region called a gap junction. So again, we
have here a gap junction and then a close-up of a gap junction over here.

At electrical synapses, the space between the presynaptic and postsynaptic neurons is much smaller
than in chemical synapses; it’s only about 2-4 nanometers across. And the pre- and postsynaptic neurons
are actually connected by protein structures called gap junction channels. So these gap junction channels
create a pathway that connects the pre- and postsynaptic neurons, and allows electrical impulses in the
form of charged particles called ions, which are represented by these blue dots here, to flow from one
neuron to the next.

So this is basically an extension of the electrical signaling that travels down the axon of the neuron, but it
enables that message to pass from the presynaptic neuron to the postsynaptic neuron. While electrical
synapses are not common in humans, they do offer some benefits. Transmission at these synapses is
very fast, in fact it’s virtually instantaneous. While chemical synapses are fast as well, they do involve a
slight delay, and there’s essentially no delay at all at an electrical synapse.

Communication across electrical synapses can also typically occur in both directions, meaning the
presynaptic neuron can send signals to the postsynaptic neuron and vice versa. This enables electrical
synapses to be useful in synchronizing electrical activity among groups of neurons.

There are neurons, for example, in the brainstem that are involved in regulating breathing and they use
electrical synapses, which ensures they’re working in a synchronized manner. One major benefit of
chemical synapses, however, is that they can amplify signals substantially.

A relatively weak electrical current in the presynaptic neuron can cause the release of thousands of
neurotransmitter molecules at a chemical synapse, and those neurotransmitter molecules can cause a
substantial effect on a postsynaptic neuron.
So this is likely one reason for the prevalence of chemical synapses in the human nervous system,
although both types of synapses have their place.