What’s 1000 times thinner than a piece of
paper, more numerous in you than grains of sand on a beach, and proof that the smallest
things can sometimes be the most powerful? I’m talking about the synapse -- the meeting
point between two neurons. If your neurons form the structure of your
nervous system, then your synapses -- the tiny communication links between them -- are
what turn that structure into an actual system. Because, as great and powerful as your neurons
are, when it comes down to it, their strength and their purpose lies in their connections.
A single neuron in isolation might as well not exist if it doesn’t have someone to
listen or talk to. The word “synapse” comes from the Greek
for “to clasp or join.” It’s basically a junction or a crossroads. When an action potential -- and if you don’t
know what an action potential is, watch the last episode -- sends an electrical message
to the end of an axon, that message hits a synapse that then translates, or converts
it, into a different type of signal and flings it over to another neuron. These connections are rather amazing feats
of bio-electrical engineering, and they are also ridiculously, mind-bogglingly numerous. Consider that the human brain alone has 100
billion neurons, and each of those has 1000 to 10,000 synapses. So you’ve got somewhere between 100 to 1,000
trillion synapses in your brain. Each one of these hundreds of trillions of
synapses is like a tiny computer, all of its own, not only capable of running loads of
different programs simultaneously, but also able to change and adapt in response to neuron
firing patterns, and either strengthen or weaken over time, depending on how much they’re
used. Synapses are what allow you to learn and remember. They’re also the root of many psychiatric
disorders. And they’re basically why illicit drugs
-- and addictions to them -- exist. Pretty much everything in your experience
-- from euphoria to hunger to desire to fuzziness to to confusion to boredom -- is communicated
by way of these signals sent by your body’s own electrochemical messaging system. Hopefully, you know enough about email and
texting etiquette to know that if you’re gonna communicate effectively, you have to
respect the sanctity of the group list. It’s not a great idea to send a mass text
to all of your friends first thing in the morning to give them the urgent news that you
just ate a really delicious maple-bacon donut. Seriously, people. If you happen to have a friend who
truly adores bacon, then an email would suffice. But! If you’re out clubbing and suddenly
Bill Murray shows up and starts doing karaoke... then that would be a totally appropriate time
to notify all of your friends at once that something awesome is happening and they better
be a part of it. And in much the same way -- OK, in kind of
the same way -- your nerve cells have two main settings for communicating with each other,
depending on how fast the news needs to travel. Some of your synapses are electrical -- that
would be like an immediate group text. Others are chemical synapses -- they take
more time to be received and read, but they’re used more often and are much easier to control,
sending signals to only certain recipients. Fortunately, your nervous system has better
text etiquette than your mom, and knows when each kind is appropriate to use, and how to
do it. Your super fast electrical synapses send an
ion current flowing directly from the cytoplasm of one nerve cell to another, through small
windows called gap junctions. They’re super fast because the signal is
never converted from its pure electrical state to any other kind of signal, the way it is
in a chemical synapse. Instead, one cell and one synapse can trigger
thousands of other cells that can all act in synchrony. Something similar happens in
the muscle cells of your heart, where speed and team effort between cells is crucial. This seems like a good system, so why aren’t
all of our synapses electrical? It’s largely a matter of control. With such
a direct connection between cells, an action potential in one neuron will generate an action
potential in the other cells across the synapse. That’s great in places like your heart, because
you definitely don’t want a half a heartbeat. But if every synapse in your body activated
all of the neurons around it, your nervous system would basically always be in “group
text” mode, with every muscle fiber and bit of organ tissue always being stimulated
and then replying-all to the whole group which would stimulate them even more until everyone
just got maxed out and exhausted and turned off their phones for good...which would be
death. So that would be bad, which is partly why
we have chemical synapses. They are much more abundant, but also slower, and they’re more precise
and selective in what messages they send where. Rather than raw electricity, these synapses
use neurotransmitters, or chemical signals, that diffuse across a synaptic gap to deliver
their message. The main advantage chemical synapses have
over electrical ones is that they can effectively convert the signal in steps -- from electrical
to chemical back to electrical -- which allows for different ways to control that impulse. At the synapse, that signal can be modified,
amplified, inhibited, or split, either immediately or over longer periods of time. This set-up has two principal parts: The cell that’s sending the signal is the
presynaptic neuron, and it transmits through a knoblike structure called the presynaptic
terminal, usually the axon terminal. This terminal holds a whole bunch of tiny
synaptic vesicle sacs, each loaded with thousands of molecules of a given neurotransmitter. The receiving cell, meanwhile, is, yes, thankfully
the postsynaptic neuron, and it accepts the neurotransmitters in its receptor region, which is
usually on the dendrite or just on the cell body itself. And these two neurons communicate even though
they never actually touch. Instead, there’s a tiny gap called a synaptic cleft between them --
less than five millionths of a centimeter apart. One thing to remember is that messages that
travel via chemical synapses are technically not transmitted directly between neurons,
like they are in electrical synapses. Instead, there’s a whole chemical event
that involves the release, diffusion, and reception of neurotransmitters in order to
transmit signals. And this all happens in a specific and important
chain of events. When an action potential races along the axon
of a neuron, activating sodium and potassium channels in a wave, it eventually comes down
to the presynaptic terminal, and activates the voltage-gated calcium (Ca2+) channels
there to open and release the calcium into the neuron’s cytoplasm. This flow of positively-charged calcium ions
causes all those tiny synaptic vesicles to fuse with the cell membrane and purge their
chemical messengers. And it’s these neurotransmitters that act like couriers diffusing across the
synaptic gap, and binding to receptor sites on the postsynaptic neuron. So, the first neuron has managed to convert
the electrical signal into a chemical one. But in order for it to become an action potential
again in the receiving neuron, it has to be converted back to electrical. And that happens once a neurotransmitter binds
to a receptor. Because, that’s what causes the ion channels to open. And depending on which particular neurotransmitter
binds to which receptor, the neuron might either get excited or inhibited. The neurotransmitter
tells it what to do. Excitatory neurotransmitters depolarize the
postsynaptic neuron by making the inside of it more positive and bringing it closer to
its action potential threshold, making it more likely to fire that message on to the
next neuron. But an inhibitory neurotransmitter hyperpolarizes
the postsynaptic neuron by making the inside more negative, driving its charge down -- away
from its threshold. So, not only does the message not get passed along, it’s now even
harder to excite that portion of the neuron. Keep in mind here: Any region of a single
neuron may have hundreds of synapses, each with different inhibitory or excitatory neurotransmitters.
So the likelihood of that post-synaptic neuron developing an action potential depends on the sum
of all of the excitations and inhibitions in that area. Now, we have over a hundred different kinds
of naturally-occurring neurotransmitters in our bodies that serve different functions.
They help us move around, and keep our vital organs humming along, amp us up, calm us down,
make us hungry, sleepy, or more alert, or simply just make us feel good. But neurotransmitters don’t stay bonded
to their receptors for more than a few milliseconds. After they deliver their message, they just sort of pop
back out, and then either degrade or get recycled. Some kinds diffuse back across the synapse
and are immediately re-absorbed by the sending neuron, in a process called reuptake. Others are broken down by enzymes in the synaptic
cleft, or sent away from the synapse by diffusion. And this mechanism is what many drugs -- both
legal and illegal -- so successfully exploit, in order to create their desired effects. These drugs can either excite or inhibit the production,
release, and reuptake of neurotransmitters. And sometimes they can simply mimic neurotransmitters,
tricking a neuron into thinking it’s getting a natural chemical signal, when really it’s
anything but. Take cocaine, for example. Don’t take cocaine. Once it hits your bloodstream, it targets
three major neurotransmitters -- serotonin, dopamine, and norepinephrine. Serotonin is mainly inhibitory and plays an
important role in regulating mood, appetite, circadian rhythm, and sleep. Some antidepressants can
help stabilize moods by stabilizing serotonin levels. And when you engage in pleasurable activities
-- like hugging a loved one, or having sex, or eating a really, really great donut -- your
brain releases dopamine, which influences emotion and attention, but mostly just makes
you feel awesome. Finally, norepinephrine amps you up by triggering
your fight or flight response, increasing your heart rate, and priming muscles to engage, while
an undersupply of the chemical can depress a mood. So in a normal, sober state, you’ve got
all these neurotransmitters doing their thing in your body. But once they’ve delivered
their chemical payloads, they’re usually diffused right back out across the synapse
to be absorbed by the neuron that sent them. But cocaine blocks that reuptake, especially
of dopamine, allowing these powerful chemicals to float around and accumulate -- making the user feel
euphoric for a time, but also paranoid and jittery. And because you have a limited supply of these
neurotransmitters, and your body needs time to brew more, flooding your synapses like
this eventually depletes your supply, making you feel terrible in a number of ways. Cocaine and other drugs that target neurotransmitters
trick the brain, and after prolonged use may eventually cause it to adapt, as all those synapses
remember how great those extra chemicals feel. As a result, you actually start to lose receptors,
so it takes even more dopamine, and finally cocaine, to function normally. Sometimes the best way to understand how your
body works is to look at how things can go wrong. And when it comes to your synapses,
that, my friends, is what wrong looks like. In their natural, healthy state, your synapses
know when to excite, when to inhibit, when to use electricity and when to dispatch the
chemical messengers. Basically, a healthy nervous system has the
etiquette of electrical messaging down to, well, a science. Today you learned how electrical synapses
use ion currents over gap junctions to transmit neurological signals, and how chemical synapses
turn electrical signals into chemical ones, using neurotransmitters, before converting
them to back electrical signals again. And you learned how cocaine is a sterling example
of how artificial imbalances in this electrochemical system can lead to dysfunctions of all kinds. This episode of Crash Course was brought to
you by Logan Sanders from Branson, MO, and Dr. Linnea Boyev, whose YouTube channel you can check out in the description below. Thank you to Logan and Dr. Boyev for supporting Crash Course
and free education. Thank you to everyone who's watching, but especially to our Subbable
subscribers, like Logan and Dr. Boyev, who make Crash Course possible. To find out how you can
become a supporter, just go to Subbable.com. This episode was written by Kathleen Yale,
the script was edited by Blake de Pastino, and our consultant, is Dr. Brandon Jackson.
It was directed by Nicholas Jenkins and Michael Aranda, and our graphics team is Thought Café.