This articles is going to explain, in mild to moderately entertaining format, the basics of how our brains work1, and how they sometimes don’t. The challenge to myself is to do it from memory.2 This is also my foray into paid content. So the idea is I’m going to write things, like this piece, which will presumably not be opinion pieces, although I will, likely, express opinions. But it’s really like more a “fun” version of a textbook of medicine, one chapter at a time. Some portion of the way through this tantalizing piece of explaining, there’s gonna be a paywall. Here’s a pro tip. If you sign up, you get to keep reading, because I’m going to auto comp you. I’m not gonna make you pay for it. Not yet anyway. It’s just gonna make you sign up for my subscription list. But eventually, behind that paywall, there’s content. Might it be that people might want because it teaches them something useful? The idea is not to make my readers want to choke on their own tongue out of sheer boredom. It is an experiment. Your feedback, as ever, is welcome.
In my last article (on the medicine Auvelity) the existence of this piece was foreshadowed. We’re gonna start from neurons, and work our way up from there, that pretty soon, you’re gonna understand science and medicine just as well as I do. And then your bull💩 antennae will be more finally tuned than they are now. You’ll also be prepared to impress your friends.
The Neuron:
Your body has a lot of neurons in it. Most of them aren’t in your brain. That’s true. The majority of the neurons in your body are actually in your gut.3 Your intestine, particularly your small intestine, has a really important job that requires a coordinated dance of activity, called peristalsis. This is the rhythmic contraction of the smooth muscle cells of this tube in order to move food on its way. This dance is choreographed by the neurons of the enteric4 nervous system. They are the same basic nerve cells that you have in your brain, but the enteric nervous system functions largely with serotonergic neurons, this is to say that the serotonin neurotransmitter, pictured here:
It is doing it most of the talking. And will get to what that talking is in just a minute.
The Structure of a Neuron
Neurons structurally have a cell body. This is where the bulk of the machinery of any given cell lives. There are inputs to nerves, which we called dendrites. There are outputs, and usually it’s one output, although that one output can have a bunch of different endings coming off of it. So basically if you took a tulip, and laid it on its side, you’re looking at what a neuron looks like. The roots are the dendrites, information comes in from these. There is a bulb, and there is a long projection— this is called an axon —through to the flower at the end. The flower in this context is is the presynaptic terminal, and there is a post synaptic terminal on the dendrite on the other side of a gap. This little gap is called the synapse.
The nervous system is taking a bunch of nerves and connecting axons and dendrites of different nerve cells with little gaps in between them. They talk to each other by having neurotransmitter, think of the pollen in a flower, float across the synaptic cleft (space between two nerve cells) to “pollinate” the dendrite on the other side.
Communication Between Neurons
We spend a lot of time in psychiatry and in the popular media talking about this tiny little bit of communication between two cells. This synaptic cleft takes up most of our mental space, If you will pardon the pun. We talk about neurotransmitters5 and brain chemistry all day long. I would argue this is actually a sideshow. The really important stuff happens within the cell itself. Neurotransmitters are just a way of bridging from one cell to the next. But most medication is a way to alter neurotransmitters, and so at least from the standpoint of pharmaceutical companies, talking about neurotransmitters makes their drug seem important.
Inside the Neuron
So what’s going on inside those cells? The answer, in its simplest form, is math. Cells are calculators. They are doing addition and subtraction on the impulses that come in, some of which are excitatory, and some of which are inhibitory. This means there are pluses and there are minuses. If you get enough pluses, they add up to a cell firing, and conducting its own electrical signal down an axon, which leads to a signal to the next cell it projects to via neurotransmitter. If you get enough minuses, they cancel out the pluses. And the cell doesn’t fire. Inside of the cell, this math is done with electrical voltage. That’s right, it’s all electricity in there. OK, so it’s electricity and electrical potentials, which is what voltage is, and just liking batteries, these electrical potentials, differences in voltage, are maintained through different concentrations of ion. When I say ions, think salt.
The Salts’ the Thing
Sodium, potassium, chloride, ions6. In fact, those are the main ions were gonna talk about. Every kind of cell, not just neurons, maintains differences in concentration inside of a cell membrane compared you outside of its cell membrane. These differences in concentration are what make it possible for cells to be living things at all. If everything was the same inside and out, there would be no energy for the cell to do anything. So having a cellular membrane across which you can keep things differently concentrated is the key to life.
But if it sounds like our cells are just made up of salt water, that’s because they are. We have the ocean inside our neurons, and our blood is basically the Atlantic. We are from the oceans, and we carry that ocean water with us wherever we go. It’s little differences in 1. how salty and 2. what kind of saltiness that make life possible.
So it turns out that when you have a cellular membrane, you can take sodium and move it one way, and potassium, and move it the other way. And that’s one of the most important functions in a neuron, there is a protein called the sodium-potassium pump, and it converts energy in the form of ATP, adenosine triphosphate, the basic energy molecule in cells, into stored energy in the form of different amounts of sodium and potassium on the inside of the cell and the outside of the cell. Now astute observers will remember that sodium and potassium are on the far left of the periodic table.
The leftmost column starts with hydrogen, one step down is lithium,
one step further down is sodium,
and one further step down is potassium.
The symbols for these elements, for those who have been out of chemistry class for a long time, are Li, Na, and K. And because they are all on the far left of the periodic table, they all have a one little + next to them in terms of their charge (when one electron is removed from their outer most electron shell, leaving them as ions). Because sodium and potassium are both positively charged ions, and have the same amount of charge, it wouldn’t work to just have the same amount of sodium inside the cell as there was potassium outside the cell from an electrical potential perspective. This would be the same total amount of charge on both sides. If you want the charge to be different, the concentrations of these ions have to be different. You need more pluses on one side then on another side. And then there is a relative difference in the amount of positive charge in one place versus the other place.
It’s the change in the concentration of these ions that allows for the mathematics7 that cells are doing on our behalf. If we get enough excitatory8 signal, neurons, which are at a negative resting potential most of the time, become slightly more positive9. The resting potential when neurons are just hanging out and doing their thing is around -70 mV.
The name in science for these nudges towards firing—and not firing—for a cell are called excitatory presynaptic potentials and inhibitory presynaptic potentials, or EPSPs and IPSPs for short. Essentially, a neurotransmitter floats along from the Beautiful tulip flower of another neuron into the other side of that tiny gap, which an our tulip metaphor is a root, And it creates either an EPSP or an IPSP.
Now, I called neurons calculators, and they basically are, but they are adding up or subtracting towards just one outcome: if the cell gets positive enough, the neuron fires10. In this way, neurons are like any process that has a lot of input, but only one output. Peeing. You’re either peeing or you’re not peeing. You can have the urge to urinate, or in science terms, the urge to micturate, because we don’t want to say the word Pee.11
So after enough EPSPs hit a neuron, and not enough IPSPs come in at the same time, the voltage of the inside of the cell gets more positive, which was call Depolarized. It’s important to understand that the cell membrane itself is relatively permeable12 to potassium and not very permeable to sodium at baseline, and so there is leakage of both sodium and potassium happening all the time, but more potassium than sodium leaks. And therefore the sodium-potassium exchange pump keeps creating this swap in concentration that leads to a voltage difference. This powered by energy, as mentioned before, in the form of ATP:
The Excitement, and the Charge, Builds!
So we have a situation where as more and more of the positive charge buildup inside the cell the resting potential increases from -70 mV upwards. Now there are three more ion channels that will get introduced at this point, and the most immediately important of which is the voltage gated sodium channel that at a certain level of depolarization slams open all of a sudden, and all at once. These voltage gated channels all opening at once create a massive influx of sodium into the cell, and this creates a huge depolarization.
Action (potential) Time!
We call this voltage spike an action potential13. This action potential, a wave of depolarization, moves down the length of the axon — this is the large stem of the tulip—until it hits the axon terminal. When this action potential gets where it’s going, the depolarization triggers the release of neurotransmitter that’s sitting around in little bubbles holding neurotransmitter inside. These bubbles called vesicles hang out in the axon terminal just waiting to be released. The neurotransmitter molecules that were hanging in the bubbles, they get spilled into the synaptic cleft. They then then float their way across the synaptic cleft, and will bind to receptors on the dendrite of the next neuron over.
A Conversation, in Chemical Format
And that is how two neurons talk to each other. Each neurotransmitter hitting the postsynaptic side of the terminal, the dendrite of another neuron, goes on to creates either an IPSP or an EPSP, depending on what kind of neuron and neurotransmitter we’re talking about.
And that, dear readers, that is how a nerve fires.
If you’ve enjoyed this post, and you’d like more, please feel free to let me know in the comments. You get to ask for scientist to write the neuroscience textbook that you want to read!
Reviewing terms, so my readers can really nail their multiple-choice tests or make necessary flashcards pretty quickly:
Neuron: the nerve cells we spent the whole article talking about, and we have left out all of their support system which we called ganglia. These are also cells, and they are crucial to the function of the nervous system, because they support the neurons which are prima donnas.
Axon: Long part of the nerve down which the action potential travels.
Depolarization: the inside of the nerve cell getting less negative/more positive than the -70 mV resting potential that is where the hang out usually.
Dendrite: many many inputs to the cell, that synapse on the axons of other cells
Synapse: a connection between two cells, on one side of the axon, on the other side of the dendrite.
Synaptic cleft: the empty space between the axon of one nerve and a dendrite of another, and between those two structures in this little gap we have a synapse.
Neurotransmitter: molecule with a specific shape that nerves used to communicate with each other.
IPSP: inhibitory postsynaptic potential —that makes the cell less likely to fire
EPSP: excitatory postsynaptic potential —that makes the sale more likely to fire
Vesicle: little bubble in the axon terminal that holds neurotransmitter before it gets filled out into the synaptic cleft as the result of an action potential.
Receptor: specifically shaped proteins on the postsynaptic side of the synaptic cleft into which a neurotransmitter binds. 14
Action potential: the rapid and massive depolarization that starts at the base of an axon, called the axon hillock, by the action of voltage gated ion channels snapping open if the depolarization from the incoming EPSPs reaches a certain threshold, this causes kind of a chain reaction of voltage gated channels opening all the way down the axon, and this is a little bit like voltage gated channels doing the wave. This conducts electricity, for all practical purposes, down the axon from the body of the cell to the axon terminal.15
Monoamine Neurotransmitters: serotonin, dopamine, epinephrine, norepinephrine. To make things more confusing, the British have different names for Epinephrine and norepinephrine which are adrenaline and noradrenaline. These are the same things. of note, I looked up monoamine neurotransmitters to make sure I wasn’t forgetting any, and the answer was I wasn’t.
Yes this is educational in intent.
I wanted to make it kind of engagingly weird , so I decided to do it “from memory*” is one of the best ways of doing that. I’m not referencing notes before hand, I’m just using the very brain I’m talking about to remember Steph and explain it. There may be some fact checking after the fact, if I’m not sure about something, and frankly, I’m just gonna admit that if it happens, because I’m gonna feel embarrassed, and I don’t want you to feel embarrassed, and the best way to do that is to model embarrassment by embarrassing myself, which frankly I’m very good at. I am to self embarrassment what my prior sentence is to run-on‘s: really really good at being the thing that they are.
*It’s also transparently a flex to do it from memory, I have a good one, and I’m not gonna pretend I don’t, and I want you to think I’m smart, so you keep reading this. But I am actually doing this from memory. Mostly because I can. But also because it forces me to do it faster and without making it boring by micromanaging it and looking stuff up constantly. Yes it’s a conceit. Yes it’s conceited. Let’s hope it works! Says the guy who just had the asterisk in the footnote.
Gut, singular, Long tube through which food goes and is absorbed. lips, oral pharynx, pharynx, esophagus, stomach, duodenum, small intestine, large intestine, rectum, anus, and out into the toilet. That’s the gut journey. Hope you enjoyed it.
Enteric meaning “in your gut”— entertaining late, given the gut is a very long tube, the plural of gut— guts— refers to the same thing that gut does. The pluralization of the term good just refers to the fact that people have no idea that the tube that they’re saying lived around itself is really one tube and shouldn’t be plural at all. Pluralization police, I hope you’re happy.
In fairness, on the part of the pharmaceutical companies who did some excellent marketing around specific neurotransmitters, mostly we talk about monoamine neurotransmitters. MonoAmine > means carbon containing molecule that has a nitrogen in it but only one of those. Mono equals “one” and amine equals “with nitrogen”. This is some real propaganda work on the part of Pharma, because the monoamine transmitters are relatively minor players in terms of overall volume of neurotransmission. Although that’s what we’re modifying the transmission of with most of the drugs we have bought and sold in psychiatry for a long time. They are only a part of the story and frankly the smallest part. Buckle up kids, it’s going to get Sciency. glutamate is the primary excitatory neurotransmitter, so there’s a lot of that going around. GABA is the primary inhibitory neurotransmitter. There are, of course, others.
Ion: atom with an electron removed, so that it is positively charged. See also: cation. Or an electron added so that it is negatively charged. See also: anion
Addition and subtraction people. This is not a complex stuff.
Closer to firing
Less negative. This is in the direction of more positive, but it does not mean that the actual voltage is a positive voltage, it’s still negative if they cell hasn’t fired.
We are talking membrane resting potential that is above -70 mV, like -65 mV, -60 mV, those are all more positive because the amount of negative charge is less. and that is a relative voltage, which is made up of a bunch of positive charges of which there are different amounts. Yes that’s really complicated. But I didn’t make up nature, that’s just what’s happening. We’re building brains out of ocean water. Give me a break.
But Micturition, although there is a volumic calculation that can be done, is its self categorical: it’s either happening or it’s not. You can have the urge. You can do a peepee dance. You can do more of a peepee dance like a six-year-old who just got out of the car and really needs to go, and really needs to let you know theyreallyneedtogo. You can hold it really well. But at the end of the day, the outcome is either happening or not happening. That’s what neurons are like. Firing or not firing, but in the middle, they may do a little neuron dance as they get closer and closer to that categorical outcome.
Permeable: things can get through it. Opposite of impenetrable, impermeable, Blocked, etc.. impermeable: thou shall not pass. Permeable: come on in, it’ll be fine, just not all at once, take your time. #NewWords
I think this is just an awesome name. There is the potential for action. The action potential is so promising. I just love it.
This is a slight oversimplification, there are actually presynaptic receptors and auto receptors on the cell that’s doing the firing of the action potential, so I can regulate its own behavior. But that’s getting a little bit too much into the weeds.
We didn’t really get into glial cells yet, but in the brain, axons are surrounded by insulation. This insulation is called myelin. There are gaps between different sections of insulation. The insulation serves the same purpose it does in electrical wires, to increase the speed of the conduction of electricity down the axon. In the case of axons, the increase in speed is to do with the property we refer to as Salatory conduction – this means basically the depolarization that can hop from one uninsulated section to the next. These uninsulated gaps are called nodes of Ranvier. “The salutary conduction of an action potential from node of Ranvier to the next node of Ranvier” is definitely the answer to some exam question you’re going to get if you’re learning about this for a class. The illness we know as multiple sclerosis is essentially the result of an autoimmunic attack on that myelin insulation, which blows up this rapid conduction system, because once you get rid of the myelin, you don’t really have nodes anymore, and once-rapid conduction becomes so slow it becomes nonfunctional in the central nervous system and you get all sorts of problems.