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  • 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 wordsynapsecomes from the Greek forto 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 youve 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 theyre used.

  • Synapses are what allow you to learn and remember.

  • Theyre also the root of many psychiatric disorders.

  • And theyre 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 youre

  • 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 youre 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 theyre

  • 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.

  • Theyre 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 ingroup textmode, 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 theyre 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, youve got all these neurotransmitters doing their thing

  • in your body. But once theyve delivered their chemical payloads, theyre 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.