Molecular Neurobiology (BRAIN CHEMICALS) with Crystal Dilworth

Oh hey, it's the lady who keeps candles in her wallet because you never know when you're going to be in a pinch. And assume me someone's birthday, and then you'll be more excited about singing to them than they'll be excited about being sunk to Ali. Ward back with another episode of Ologies. Okay, you like brains? Does your brain like brains? It probably does so right now, your soft, squishy think lump is just hanging out in your head.

So I came out of the room and my committee was still in there deliberating, And normally that is one of the scariest moments in anyone's life because you're not sure what they're going to say.

But I was.

I was pretty sure because my committee chair had been like, we're just going.

To chat for a little bit, we'll be right out.

They came out and they shook my hand and they said congratulations, doctor Dilware, and I got an entirely new lease on life. Oh my god, like everything changed.

Did you know growing up that you were going to be a doctor or a neuroscientist. I mean, you are really good at a lot of things, and I think that that sometimes is difficult.

No, I was going to be a dancer. I was going to be on stage at Lincoln Center. Just like all of the books that I had read about how to be a professional ballet dancer had nothing to do with science really.

And then, so were you studying ballet and then sneaking into chem classes? How did it work?

Who were you cheating on scholastically? I think the decision to go to grad school. I was definitely cheating on my dance classes. So I was in professional dance school in New York City doing the things that you have to do to be a professional dancer, and I just wasn't fulfilled by the experience. I think it's really hard. I was lying about my age so that I could

Yeah, and I.

Was looking for an opportunity to be an adult and to be treated like I had something to intellectually contribute. I wasn't getting that in my artistic life. So I started skipping my classes and taking the subway uptown to Columbia and attending the chemistry department lectures, which is insane now that I look back on it now, like nobody goes to those lectures voluntarily, Like the grad students are

Wait, they give pizza out of these things. Otherwise nobody goes.

Yeah, most of those like weekly lectures are accompanied by some type of bribe.

So why neuroscience. Well, I guess.

I was always interested in people and their behavior because maybe as a homeschooled kid that didn't have like a really diverse social network. I mean I had a social network, but not the diversity that you wouldn't see in like public school, for instance.

Some people's their behavior.

Seemed unfathomable to me, like I just don't understand, like what is this programming and how does it work?

And so I thought, oh.

Maybe I would study history, maybe I would study sociology or psychology. And my dad said no, no, he was like, that's not a real science. None of those are real sciences, and you have to choose a real science.

What was your dad? Did your dad study?

Saying he yeah, his background is in physics. My mom's background is in microbiology. That was what they understood, okay, And I don't think they were afraid of all the things the parents are afraid of, like she's never going to get a job, she's going to be destitute, she's going to move back home with.

My mom right now.

By the way, so FYI best laid plans of my cin men.

Yes, but you're like an international traveler and you're like about to move to Sumatra.

Yeah it's true, Yeah it's there are reasons also that I decided to move in with my mother to help take care of her as well.

But you know, like I said, this is their plan. But so brains, like, do you start with molecular biology when you decide? Okay, I want to figure out how this weird big lump of stuff in my bone bowl in my head works? Like where do you even begin with that? Do you start with like neural anatomy? Do you start with chemistry of it? Like?

For me, the eureka moment was I was taking organic chemistry because you know, typical freshman okem when everybody has stake. And I was also taking biopsychology, which is the closest I could get to a psyche class and still like, have this be approved? And I should like clarify that I started college really young, so I was probably fourteen or fifteen at this time, so my parents were still approving my course load, so I was restricted in what courses I could take based on their approval.

Oh my god, wait, I've known you for four years and I did not know that you started college at fourteen or fifteen. Yeah.

Yeah, I started at a junior college, which you know, your first two years are the types of courses st're able to take there. And I transferred to a four year college much later.

Oh my god, I don't think I was wearing a broad at fourteen. I wasn't either. Your parents would have obviously like, help you figure out what courses you're going to take, so biopsychic.

Yeah, it's kind of backfired because I was in biopsych and they laid out in the book and in the lecture the pictures of the different neurotransmitters, the chemicals in our brain that sort of determined the brain functionality that

And that was like the aha moment. If you're like, quick, word, what is it benzene ring? It's not an oil gang, but more elementally, it's six carbon atoms that are joined in a ring with a hydrogen atom stuck to each and she was like, ah, my brain loves this stuff. Now. Her bachelor's and biocam and so far, most of her college courses were more generally about the human body chemistry and didn't focus on the thinky parts of the human body as much.

So I didn't really go back to focusing on the brain until my senior year. So all of my upper division electives were in neuroscience, and that's when I was like, Oh.

This is how I want to apply these things. What, okay, stupid question. What is the difference between neuroscience, neurology, neurobiology, molecular neurobiology. I feel like if you don't work with brains, you're like, oh, olks, kind of call it a neuro something or other. Like what are those different fields mean?

Okay, So I'm going to take you on a little journey. Okay, I am a first year graduate student. I have not yet chosen a lab I am. I'm at cal Tech. Every single person that I'm meeting is smarter than me. I am incredibly intimidated and anxious and like, really really need to do a good job otherwise I'm going to fail life. And I go into my first meeting with the professor that's going to be my PhD thesis advisor.

And he's like, I'm going to stop you right there, I'm let you finish.

Oh God, if you're interested in neurology, then you should be going to meet. We don't do neurology here. Neuroscience is the science behind the brain, and we do research on how the brain works, and we get PhDs and that's the type of science that we can do on the brain. Here are you still interested? And so that is the difference. God, I would have had immediate reactive diarrhea and just excuse myself from life. I would have

So what is a neurologist exactly. Okay, they are physicians, medical doctors with mds, probably stethoscopes, I don't know who treat neurological diseases and disorders that affect the nerves and spinal cord and of course the brain. So you can show up in their office and say, please talk fix me. That is a neurologia. I honestly don't know about the deethoscopes. I just made that up. They might not even need them, but you get the general aesthetic, and a neuroscientist.

Studies the science behind how the brain works and why the brain works, so you have to have knowledge of some of that stuff, but it's mostly like hypothesis driven investigation. Okay, So a brain, what is it? What is this big? Is it mostly fat?

What is it? Is it proteins? What is it made of? Yeah, it's all those good things.

It's all fats and proteins and carbohydrates all smushed together into a collection of different types of cells.

There's like eighty.

Billion neurons and they're all sort of smushed together, and there's different types of those neurons, those brain cells, and they're clustered together in different areas, and those different areas have specific functions that all have to work together, and that sort of what we think of as that like the orchestra of the brain as an organ.

But that's like not even it. But wait, there's more.

There's like a whole other layer of cells we call them glial cells or astrocytes that help those neurons to function. Oh so it's not just neurons, but there's like a whole other set of support cells. And they're not even really support cells because they doing really important stuff.

And what are the astrocytes and glial cells do? They do so many things.

So my favorite type of support cell is the cell that creates myelination around electrons. So that's like little wire insulators to help the electric part of the signal go faster down the axon of the neurons, so I can like send if I'm a cell in your cell, and I can send my message to you like way faster because of the insulation. And that's actually one of the

So glial cells are a support cell and glial means glue because it was thought that glial cells just kind of held all the neurons together, kind of like a bunch of mashed potatoes around a pile of yarn. But they do so much more than that. And there are different types that do different things. We won't go into all of them. But the astrocytes are starry shaped, hence astro and they give nutrients to neurons, they help repair damage,

They can be long, they can be short, but the critical parts of the neuron are the cell body, which is where all the good stuff happens, just like a normal cell, and the axon, which is sort of like that long wire that connects one end to whatever other cell it wants to wants to talk to. There's projections both from on each side of the neuron. Those would be considered like dendrites, and those dendrites create the connections which we call synapses that are house cells talk.

To each other. So it's like sort of the main main parts. So neurons, they're a cell with a sometimes long axon to reach out to other cells and little fingery dendrites at the end. And you may remember the dentrology episode with Casey Clapp about trees so just think of those little branches at the end of the neurons. Those are dendrites. They also kind of look like if a bird had a bunch of toes and then those toes had toes. That's your brain. Okay, So how are

My favorite part of neuroscience is the fact that neurons use both electricity and chemicals. Oh it's like communication. Okay, Oh, tell me about that.

So the really.

Important part of neurons is that there's like all of these little gates that are like regulating the ions flowing in and out of them.

And like ions are.

Like magnesium, calcium, sodium, these are really chlorine. Theose are really important, and they're just like constantly moving back and forth. But because all of those ions are charged, you get like a little electrical fear from each of the different cells. And so if I wanted to pass a signal to you, it would start as an electrical field that goes all the way down my axon due to the opening and closing,

Oh my god. And how many cells are doing this all the time in our brain lumps?

So I don't know how many cells would be active at a given time because it really depends on what we're doing. But if you think there's like eighty billion neurons and then there's like estimate like one hundred trillion synapses, oh my god. Because it's not necessarily one synapse per or two synapses per cell. You can have more connections. So this is a lot. Yeah, we're talking.

The final number is a shit ton many many zeros. Yeah, okay, and so neurotransmitters, this is like a chemical messenger that cells are sending to each other. Yeah, and what are the main neurotransmitters. I know we hear about dopamine and serotonin and maybe neuropinephrine, but take me through some of the players here.

Yeah, so I think dopamine is like the media darling of the neurotransmitter world. You have a lot of specific chemical like the three that you mentioned, that are involved in a lot of behaviors. But then there's other types of messengers as well. So we have small like peptides like we would say oxytocin, which it's not necessarily a formal neurotransmitter, but it's really critical in modulating brain function and behavior.

For instance, oxytocin, you may have heard, is a neuropeptide, not to be confused with OxyContin, which is in opiate. But oxytocin can promote bonding and feelings of comfort and attachment with partners and members of a group, or with babies. And yes, it does increase when you pet a dog, which is why you probably would not follow around an unfamiliar goose in a park and pick up its poo, but you would for your dog and not think twice. Now onto more neurotransmitters. We use acetylcholine a lot.

So that's a neurotransmitter that I studied because of its relation to nicotine, which I'm sure we'll get to. And acetyl colin is really important because it's like the fast acting neurotransmitter, and the brains of a few need to get a cell to respond right away. Acetyl colin might be the way to go. And it's so fast acting that it's used in the body as well to like help with muscle contractions.

My god, is it like the text message of neurotransmitter, get at me? Just send me a text?

Your phone is blowing off?

And so acetyl colin can that do more than just make you happy or alert? Is? Does it? Can that send all kinds of messages to you? Yeah? It can.

So if you think we talked about the brain being groups of different types of cells, and each of those cell groups probably has like different layers of cells as well, So the complexity and the brain is really really difficult I think to imagine each of those different functional groups of cells or different parts of the brain have connections to one, if not many many others, and they're all talking to each other. That's why I kind of call

Did you use that metaphor in your PhD defense? Because I think it slaps you should have.

I didn't. I don't the orchestra of the brain. I'm sure it's not original. I think it's pretty good.

I'm going to look it up and i'll tell you if anyone else has used it. Okay, so other folks have used this, and it turns out because it's a really apt good analogy. Also, when it comes to working on brains, Crystal use data from rodent brains to try to extrapolate what was happening in human brains, including I guess her own. Did you ever have any existential crises when you were like, my brain is studying brains brains on brains on brains. Does that ever freak you out? No?

I think there's the Carl Staian quote like we are the way for the universe to know itself, and so I think that that's kind of how I feel how I feel as a neuroscientist.

Do you ever think about certain reactions you have to life or certain like if you're having a down day or an update? Are you ever thinking about like your orchestra, like your like horn sections going off right? Absolutely? You doo? Yeah, of course does that help you at all when you're relating to other people thinking Okay, well this is not just this person's a jerk, or maybe this person isn't being sad for effect, Like do you think about them as like a concert of chemicals ever?

Yeah, I think obviously I can. That's when I'm thinking, like rationally thinking and using that prefrontal cortex to try and compose a logical flow around why somebody.

Is behaving the way that they are. But you know, in an.

Everyday life, it's usually more a motion driven, reactivity driven. That's how our brains evolved, is to react to external stimuli, not necessarily to think and problem solve about them as the first thing, right, because.

You don't want to be like, is it a snake? I'm not sure.

If it's a snake, I'm going to keep walking towards it until I'm absolutely sure. Ouch now I'm dying, right, Like, that's not how brains. Our brains work. So I think when I can take a step back and think rationally about like why is this person yelling at me?

It is helpful. But that's you know, I'm human just like everybody else. And that prefrontal cortex that's right behind our forehead, and that's the kind of meteor chunk that's evolved more recently.

Yeah, that's I think that's what we'd like to think of as one of the differentiating parts of you know, human brains versus other animal brains. And I want to make a comment about animal brains in a second, But it's our ability to extrapolate, to use logic and reasoning to come up with creative solutions to problems, to not just react, and to think about downstream effects. That's what the prefrontal cortex helps us do. But what I was

The pop culture reference to the lizard brain, yes, yes, okay, okay, Okay, let's let's debunk this. Flim flam really bothers me. Okay.

I was going to ask about it because it's often one used incorrectly.

Okay.

It's usually when when people say, don't listen to your lizard brain, it's just lizard brain. I think what they mean is, don't listen to your limbic system, okay, or your mid brain or the center of your brain in

They do, yeah, they do.

It's nothing like the giant, you know, white matter that we have. It's nothing like the big, you know, prefrontal cortex that you would see in primates, but it's something that evolves similarly and when they evolved, I mean in gestational period and you see like very similar wiring there. So poor lizards, they're really getting a bad map. Also, are alligators even lizards? Back in the rology episode, I asked lizard expert Aaron McGee about.

It, stupidest question, alligators are lizards? No? No, thank you for telling me that. I just realized. I was like, how big does a lizard get? Is an alley? Why isn't an alligator a lizard? I'm sorry, it is so so much horsepucky flim flam debunked all at once. So you mentioned white matter and gray matter. What is the difference?

So white matter is all is basically the wiring, Okay, So when you would you would say, like, there's a pathway between two brain regions and that's the white matter, it's the connections, and gray matter is like more the cell bodies and the guyer, the guier stuff, okay, is.

On it kind of is there like an apple skin on a brain.

Not the way that you are describing it, But we do have a barrier between the brain and the blood system that provides the glucose and the other nutrients to the brain, and that's the blood brain barrier is critically important to protecting the brain from all the things that we're exposed to.

Can more things leak through that blood brain barrier than we realize? Are we finding that out?

Probably we used to think that it was impenetrable, and now we know that there's evidence of a lot more sort of transmission through that barrier than we think.

But it really does protect us.

I mean, think about like all of the pharmacologicals that you've ever taken in your life, and some of them can slip through, and that's good because we need them to regulate our behavior. And some of them are kept out by that barrier, which is great because they could be potentially toxic.

Okay, well, getting back to neurotransfers. Oh no, I wanted to ask if you'd ever touched a brain before, so I had to get us off course. I have touched what do you make brain?

It's very delicate, like you don't want to make a lot of relief fast food, and they're preserved brains. I haven't touched a brain of a person, which some neurosurgeons have. I cannot speak to what it's like to touch you a live brain, but one that's been preserved and formaldehyde.

It's very delicate.

It is as gooey as you think you when you're holding it, if you're anything like me, just there's an oppressive sense of responsibility that happens when you're thinking about the life that that brain was really responsible for guiding.

I don't hold it for very long.

I like held it and I kind of like felt the profound nature of what I was doing, and then and then I gave it back to the technician.

What was the setting here? What was a setting? Yeah?

Honestly, this was an undergrad at a science fair. Whoa And that was just one of the really cool exhibits, Like there were mouse brains and a human brain, and you know, like other brains that you could just kind of like touch and play with.

Wouldn't it be crazy if you don'tated your brain to science And they're like, you're just gonna go to science fairs, You're gonna recruit some people. You'd be like, what gay, sweet, shake some hands, kiss some babies, not shake some babies. We answer I will send that background. Okay, So neurotransmitters, serotonin, dopamine. Stupid question, but what do they do do they have different roles in terms of our emotions, They have very very different roles.

Okay, dopamine I'm going to start with because this is everybody loves a good dopamine story. I love, and without dopamine, we really wouldn't be motivated to do anything. So it's really interesting in computer science when they talk about computers having rewards so that you can teach it, like artificial intelligence system that you're on the right track, keep going. We have similar rewards. You're on the right track, keep going. And dopamine is how our brains have been evolved to

Okay.

Basically, whereas serotonin is more nuanced. It's not just pleasure, but it's mood and it's sleep, and it's really helping to modulate the way that those little dopamine hits are interpreted by the larger orchestra, if that makes sense.

Yeah, And what happens when they get off? Is there not enough to send a signal to the next neuron? Is there too much? And why does it seem like a very slim percentage of people have a good balance I like, or maybe it's just living in LA or Internet culture, but I feel like everyone's like, oh yeah, mirror transmitters are whack.

I'm no minor, so I mean unfortunately, I want I wanted to respond to you philosophically, Like, when we first sequenced the human genome, the lead researcher on that project was the genome that they chose to sequence. Does that mean that he's the most normal genome and every other genome is going to be compared to his? Maybe it was an arbitrary center for science to pick yea right.

Okay, so quick aside. There was the publicly funded human Genome project, and the first public genome came mostly from a single anonymous male donor. I think this would be a sperm donor from Buffalo, New York. But then aside privately funded genome research project was launched by geneticist J. Craig Ventner, who later admitted that his DNA was among

So in mental health profession, it's if you have a difference that's interfering with your ability to perform tasks in your personal or professional life, like your ability to be a part of society, then it's a difference that needs to be treated as abnormal.

Right.

So I don't know if we can say that they're necessarily off for us as an individual, but they're definitely off for us as a group of humans that all need to act together. Does that make sense? Yeah, Yeah, there's definitely differences. And those differences can come from genetics, it can come from environment. It can come from adaptations to trauma or differences in our early environment as our

And what happens if we have too much dopamine.

It seems like the more the merrier it is, the more the merrier, but it's also the way that it is dispensed. I guess, like you described it in the Addictionology episode as this like sprinkler system, right, and it's the intermittent release of dopamine that keeps us going.

Right.

If you have too much dopamine, then you're probably not motivated to do anything because you've got everything that you need. So it's kind of like what do you gift to the person that has everything right? Your system is cool, so there's no reason to do anything. In early experiments around the dopamine ergic system, they allowed rodents to just self administer stimulation to their dopamine like whenever they wanted.

But like people have.

Probably experienced this before, like you're in a really good early stage of your relationship.

You don't eat, You like your sleep's kind of disrupted.

All you want to do is like read your text messages over and over and over again, or check your phone to see if you've got another one. Your normal function is disrupted because you've got dopeamine floating around in there at levels that you're totally not used to, and there's probably some moxytocin in there as well, like really fucking things.

Oh my god. Wait, so then at what point does that decline? Is that like the two year period of like I'm over this?

Yeah, I think we get we get used to it, yeah, right, and then we can sort of like mellow out and become more normal.

The rats, some of them died.

Because they didn't They didn't eat or really do anything because they were just super happy pressing that lever for their dopamine hit.

So don't do that, just pathologically fulfilled? No, okay. Side note. I read one article that estimated four years was when dopamine starts to wane. But I really should ask a psycho neuroendocrinologist or perhaps a biological anthropologist about it. But if things are starting to feel a little stale with a partner. Some researchers think that doing scary or novel things together like I don't know, ziplining or going to haunted houses or Costco on a Saturday, those things can

If you don't have enough dopamine, it depends on what parts of your system are disrupted. But most of the classical symptoms that we see for like ADHD or depression or you know, even anxiety and in some cases usually have to do a disruption of the dopemeansys. That's why

And is that because the dopamine isn't being produced at high enough levels or it's just like not making the jump between the neurons.

That's something that is sort of on an individual basis, but I would say overall, it's probably your system isn't able to produce enough dopamine. So there's all these little like packages of the dopamine chemicals that are sitting at the terminals, like near the synapse, like just ready for the signal like release us.

We're ready to go.

And someone that has lower numbers of those little vesicles, those little dopamine packets, like even if the cell was like okay, go release all the dopamine that you have is going to be a lower level, less packages of dopamine released than like what we would consider to be a normal So.

And then what about serotonin? Then if does serotonin play a big part in depression and anxiety and ADHD as well and all of the other things that all of us.

Have the problem with the orchestra is that you can't just remove one section right like they they all work together. So yes, they're definitely serotonin is definitely implicated and pretty much like and our benefrin is imprecated in pretty much everything.

And if we inhibit.

Those little like pac man collectors, then you get more chemical in that synapse, and that raises the probability that the next cell is going to have a prolonged signal from that neurotransmitter.

Okay, so by cock blocking the neurotransmitter gobblers, there will be more in the spaces between the neurons to deliver messages. Kind of like if you canceled a neurotransmitter's lift and you just kept them at the party longer. You're like, sorry, I what can I say? We love avenue around, You're great at conversation, we love the signals. You said, this is a question that I have had for years. But I feel like I've read somewhere that neuroscientists don't really

There's look, there's so many medications and like, I'm sorry, Big Pharma, there's so many medications that we don't actually understand the molecular mechanism for. But if it works and there's the side effects aren't too bad, We're just like, just put it out there and it'll help people.

Oh my god. Okay, So we don't totally know how SSRIs work. We just know that a certain percent of people when they take them are like feeling better.

We know exactly how they work, we don't know why they work. Like, we don't know why keeping the serotonin or the noropenephrin or the dopeamin around in the synapse and increasing the signal leads to the behavioral changes.

Because the level of cox, we can.

Ask those molecular questions, like, that's the level I like to look at, because it's a lot more concrete. We can get answers there. But the multiple layers of complexity from like, well, which cells are getting the attenuated signal? And what brain regions are those cells in? Oh, but it's this brain region. But it's only those brain layers of that brain region. And what are those particular active

We don't know. Yeah. I always wondered about the lag time there, because that is the toughest. And I know that this is like a psychopharmacology question, but that is the toughest. If it's like, hey, you're depressed, take this thing, man, six weeks, there's a twenty percent chance you might feel better. You're like, you could have a lot of faith and lucky for me, like you know, well not lucky for me. But I tried a few different medications for anxiety and

Yeah, so for nicotine, it's it's super crazy, like you're actually when you're exposing yourself to nicotine, you're actually changing the way that proteins in your brain are expressing. So they're like, oh cool, I really like this. I would like it again, I would like it in a specific way. So I'm going to change the way that I'm making the proteins in my cells so that they are better able to bind and respond to this drug that I have now been exposed to and no exists in the world.

And so what does nicotine does? Does it wedge itself where a different neurotransmitter should be.

Yeah, so nicotine looks a lot like acetyl colline. Okay, So the receptors that bind nicotine also bind acetyl coline. Okay, they are called nicotinic acetyl coleine receptors. Of course, I like dominated my life for five years. But what looks similar to a protein might not actually look similar to us.

So acetylcholine is the one that's responsible for those muscular contractions. It's super fast acting. Scientists also think it may affect memory and attention. And Crystal produced from her purse two molecular models as one does. So she showed me that nicotine is a double ringed molecule with two nitrogens and acetylcholine has one nitrogen that's crowded with methyl groups, which

They look similar enough to the receptor that it responds in the same way.

Got it. So it's like when you're doing a puzzle and you find a piece that doesn't quite fit, but you can jam it in and then it fucks everything else up pretty much exactly.

It's exactly like that that I should have just said that.

That's exactly, That's exactly what's happening. And so how do some people who might be say, predisposed to that kind of addiction, how do they have a better chance at at beating it if they want to, If they're like, I'm done with you vaping, I'm done with you like cigarettes, Like what do they do well?

Beating addiction is really challenging because you have like a learning and memory component, and then you have a chemical dependence component, especially for smoking, because you'll be like, oh, I'm done, I don't smoke anymore. I am successful, and then you'll have one drink too many and suddenly you've got a cigarette in your hand and you're not exactly

In the club, we are all family.

Because you've learned that you have three drinks, then you go outside and you have a smoke. Yeah, so it's those behaviors that can really hang up recovery. Nicotine is actually one of the most substances. So I was listening to the addictionology episode that you did, and yeah, there's a lot of really really terrible withdrawal symptoms, Like withdrawing from alcohol is potentially lethal, so you need to be careful.

Okay, so what can one do? Is there any promise when it comes to like meditation and mindfulness and breathing exercise. Like, can you retrain your brain through healthier behaviors at all? Yeah, you can definitely retrain your brain. You can also through meditation, mindfulness, and cognitive behavioral therapy reduce the reason that you are smoking at all. So we see smoking behaviors especially with an ad addicts. But yeah, like if.

People that are addicted to nicotine oftentimes are in response to other things. So schizophrenics have a very specific smoking behavior. We think they're trying to self medicate. Veterans come back not even with PTSD, but just that have come back from really traumatic experiences. Possibly they're smoking in the characteristic way that they smoke to reduce activity in their amygdalah.

So you may remember the magdala from the two part errology episode, and it is a little brain nugget that I like to think of as the screaming almond of terror. So some folks may self administer nicotine to appease their shrieking almond. Does it solve problems? No, not at all, It only makes life worse. Blame your almond and then try to outsmart it.

There's lots of different indications that could cause somebody to smoke heavily that would make quitting harder.

Is that at all the same when it comes to anxiety or depression or ADHD. Are there any kind of situational triggers that might affect our levels of neurotransmitter. Yeah, that's a problem.

So we have that learning and memory, as I was saying component, So if we've learned something is dangerous to us, even if it's not, then our bodies are going to continue to respond to it that way and you have to retrain. No, that's not like some people are scared of dogs. Some people are scared of people right like you are snakes.

My mom is terrified of snakes. And it is my brother in law, and he is like a six foot four heavy metal guitarist with hair down to his waist, and he can't if he sees a snake on TV, he's like darted off. Yeap. My mom is exactly the same way. She gets like the chills because.

And then she like runs out of she runs out of the room. And so if she decided that was something that she wanted to learn to not be afraid of, there are ways through like overexposure and other therapeutic methods that I don't know anything about by no exist to rewire the brain. Probably that direct signal of snake fear is never going to really go away, but you might

And will your neurons form new pathways? Will they kind of make new channels you.

Are referring to neuroplasticity, Yes, you did. Yeah, you can definitely create new connections. We're doing that all the time. If we couldn't do that, we wouldn't be able to learn anything new, and we wouldn't be able to teach babies all the things that they need to learn in order to be competent humans.

I mean, I've got to assume that there's some of those out there.

So yes, through using particular pathways, particular connections in the brain, you can make those connections stronger. You can recruit other connections to make that pathway larger. I like to think of it as like you start out with like a hiking trail that you were told was a trail and Google Maps doesn't really have it on there, and you have need a machete and you're kind of like hacking through it.

It's a jungle in here.

But if you walk that trail many, many times, it eventually becomes much easier to use, and you can eventually become like a six lane super highway that's very very fast to go down.

And that's the preferred method because our brains are really lazy.

They don't want to do new things, they don't want to think about anything. They just want to react because that's how we stay alive. And so if you can train your brain that taking the path that you want it to take is actually easiest and allows it to be the most lazy, then you can influence the path that it chooses to take without you cognitively having to control it all the time.

So practice makes a habit kind of yes, yes, well, that's good to know. I have a gym membership that I have not used a month, and I'm like, okay, can I ask you questions for patrons? Yeah? Okay, Now, before we dive into the questions that you submitted on Patreon, a few words about sponsors who make it possible for ologies to donate to a different cause each week. Now, Crystal is once again an if then STEM ambassador for the Lena Hill Foundation, which works with a few non profits.

Yes follow up because absolutely I think that given all of the response to all the questions, you definitely need like a psychiatrist, yes on psychiatrist ologists.

This podcast is not intended to diagnose or treat. Okay, a lot of folks had questions about this Jack, Jennifer Alvarez, Eli's Anna Thompson, Grace Lauren, Rachel Thompson, panic or painick either way, Donald McGregor, Pandora to Rebecca Lynn Weisselberg, Juliana arisl And, Penny Lee and Generic Nikki all asked about ADHD. Jack said, very very plainly, I have ADHD. What exactly

So. Classically, ADHD is described as a disruption of the dopamine system, but I think that there's a lot to be said for the involvement of other neurotransmitters. We like to talk about serotonin, but I actually think that norapinephrine is more relevant to ADHD specifically because noropinephrine is responsible for attention and alertness. So when your norropinephrine system is working,

You never know when you may have to jam. And so.

The attention needed to perform and complete a task was associated with norapper nephrin sort of cycling. So there's a lot and then there's not so much, and then there's a lot, and then there's not so much. It's like just enough to kind of keep you on task and motivated.

Oh wow, Why do you think so many people have ADHD or are getting diagnosed with it? And I know so many people who are diagnosed later in life, Like where, why do you think it's so prevalent. I don't have a good answer for that.

Yeah, there's a lot of discussions people have about our technology training us to have ADHD, about the fact that we have declared a thing kind of promoting the diagnoses of it, and you know, not being able to compare it to twenty years ago to know if it really is increasing in prevalence because we've just started diagnosing it. This is an argument. This used for a lot of things.

Okay, quick aside. I looked this up and adult ADHD diagnoses rose one hundred and twenty three percent between two thousand and seven and twenty sixteen, and the prevalence of ADHD and kids went up twenty six percent. So many researchers think it's just awareness of symptoms that's driving more people to get evaluated for it. And I know so many folks with ADHD, some diagnosed in adulthood, that just

So when I learned about this, which was a while ago, we were talking about the use of amphetamines in the concept of Homeostacey's. So our entire system is designed to keep us in a certain region of activity and alertness and awakness. We want to maintain that Homeostacey's because when we get thrown out of it, we get disease and

That's why we love cocaine.

Because we love a lot of dopamine and we want that to hang around for a while, but usually ends up in really really bad results.

Right, But if you are already low on the dopamine, then it just levels you off to where maybe a neurotypical person might be, Oh, that's fascinating. So the first line of therapy for ADHD is usually medication. Why is that, well, it works in up to eighty percent of folks suffering with ADHD if the dosage is right. But the best strategy,

Right, But one of the interesting things about Homeostacey's is that it doesn't have to be like it's something that our body does naturally, and it doesn't necessarily have to be drug related. Although like the there's a really great

Oh my god, I still say we use the routine we have. Caffeine binds to the thing that makes you sleepy. It takes the place.

So caffeine interacts with adenizine receptors, and dinnersine receptors are just kind of like open and waiting for the dynzine to come. And it comes and it binds them, and if enough adentizine blinds enough of the receptors and it's like okay, we're sleepy, now we're going to.

Go to bed.

But the caffeine comes and it like sits in that binding site and prevents the adentizine from binding the receptor but doesn't activate them, so the enzine can't get in, and the receptor's like waiting for a signal that never comes and it's like, hah, you are awake now forever.

So yes, caffeine, it swoops in and it takes the seat of the sleepy chemical kind of like musical chairs, and it blocks the snoozy feelings. But what if you are staring at the ceiling and not even the fancy nancy trick of thinking of a category like fruits or cities or Star Wars characters and then going down the alphabet thinking of things in that category that start with each letter is working. Is it best to gradually taper

I don't and I don't understand the question, she says with a coffee cup.

I don't know why anyone to do that? Okay. A lot of people had questions about the genetic levels of neurotransmitters, like Bradley, Joe Portfino, Corey Navis, Kinley, Wallace Andrea essentially asked, you know, anxiety, depression, hereditary contagious. Radley asked, our imbalances in neurotransmitters more likely due to genetics or environment, speaking of someone with a whole slew of mental illnesses and addicted behaviors in my family, including myself and Radley. You're

There's so many ways that neurotransmitter levels can be affected. Definitely genetics is one of them. Definitely environment is another, and things that were temporarily going through can.

Influence it as well.

So like if you've just experienced a traumatic loss, you are going to have differences in your neurotransmitter release, but that is temporary and will eventually go back to what for you as a normal level and you're able to cope. But some people that have genetic differences, what does that even mean. It could mean we produce different amounts of neurotransmitter. It could mean that our receptors have different responses to

So genetics can influence your neurotransmitter levels for sure. But before you blame your parents for everything, a whole bunch of factors are also at play. So it's not you, fancy Nancy, it's me or Dad, or how much caffeine I drink, or maybe jet lag or the fact that I haven't been to the gym in a month. Anyway, what about SNRIs versus SSRIs, I know, Aurora, Heather Gentry, Gracie Zeca, le An Schister, Rachel Polivka, and Amelia h All wanted to know. Do we know why different SSRIs

Especially when you're talking about the interplay between depression and anxiety. And that's what I think of when I think of a combination of SSRIs and s NRIs. So we're still

Yeah. Ah, I wonder if that's why SSRIs didn't do much for me. But as a person with generalized anxiety disorder, thanks very much. An SNRI was helpful. Like what is happening with the noropenephyrin when it comes to anxiety? Like is it going off?

Is it?

Oh?

Yeah? I mean, like I was saying, nora penephrine is keeping you awake and it's telling you what focus on. So a generalized anxiety disorder, not only are you awake, but you're constantly having to focus on all the things that are chasing you, Like you're just your attention is on all the things that could potentially kill you, because your brain's trying to keep you alive, but it thinks that everything is trying to kill you, so you have

Into Australia, the land of shacks and snykes and spoil us and angreek kangaroos. I guess an angry kangaroo too? Who gives you just one star? Oh look, kangaroo two? I said your name again. You loved it. I feel like perhaps you're very empathetic too this particular. It might be that I have experienced that before, and so does an s n RI. I does it? What exactly is it doing to norop an effort if it's a selective

Yes, it can be, but it depends on the comparison levels to the other neurotransmitters. Okay, right, so you have you're trying to balance dopamine, serotonin, nora peneffrin and get that right cocktail so that you get a harmony instead of a discordant dysfunction.

If that makes sense. That doesn't make sense. I didn't realize that snrize and anxiety. Could that could be a good link. I always thought, if I've got anxiety, why do I want more goddamn nora perffor my set absence? I didn't. That was me screaming at my own brain. Yeah. So, yes, SNRIs affect both the nora pernephrin and the serotonin, and it's the balance that can be helpful. Although the first few weeks on an snri I can be rocky as hell and more stressy as your brain adjusts and then

Okay, So I'm going to assume that the reason we're talking about oreos is because there is a paper that showed that mice prefer oreos to cocaine, and then it was used in mainstream media to promote many popular but scientifically irrelevant headlines like sugar is more addictive than cocaine and a bunch of other things. So I'm just gonna substitute oreo for parmesan goldfish, which is what I eat when I was studying. And yeah, very very different things.

Let me reiterate it. Dope I mean is released to when you encountered things that keep you alive.

The nicotine completely different. So nicotine is a cognitive enhancer, so it's probably helping your prefrontal cortex function, and it's shown to help decrease anxiety. So it's probably interacting in your amygdala to reduce stress and facilitating better studying.

Okay, side note, just google oreo plus cocaine. That study is everywhere. It was cited by pretty much every news outlet in the known universe, and a professor who worked on the study stated in a twenty thirteen press release that he quote hadn't touched an oreo since the experiment, but it's unclear if that's because of their addictive implications or just because watching rats pick apart any food with their tiny clod feet for years on end tends to

Well, actually, there's been a lot of recent studies on the microbiome and the influence of food on mood, and we've always known, even before we identified that the microbiome was a thing that diet had a huge impact on mood. And of course we have always talked about sort of blood sugar activity and how crashing after a lot of sugar can influence our mood and make us depressed. But what I think that we're really asking about here is

In your bloodstream. Fancy meeting you here. Does it influence mood? Yes? Probably.

Are there particular superfoods that you can eat to raise your serotonin? Probably not, But what we eat definitely does influence the different types of microorganisms and the ratios of those microorganisms in our gut. So I can't tell her what to eat to make herself happy, But if she finds a particular type of diet that does make her happy, she's not just it's not all placebo, right, It's not just in.

Her head, in her good exactly. I think that's so bananas, that so much serotonin is made in our in our simmering poo tubes. Who knew? Who knew? It? Is crazy?

And I think about that too sometimes when I'm I'm like on a particular binge of like very very unhealthy.

Food, and I'm like, how long am I going to have to eat.

Healthy to readjust the ratios of like gut bacteria because I know that I'm feeding it a certain type of sugar or just a lot of sugar that like there's going to be overgrowth of one population, you know, of my in my microbiome, and like I'm like apologizing to the potentially more valuable and rarer bacteriums in my gut, Like I'm sorry, i know overfeeding.

That, you know. I feel like, if you like SimCity, you'll love the gut biome Oh, yes, that's so true. It's like real world consequences. For more on this topic, you can see last November's Microbiology episode with doctor Elaine Shaw, who herself says she tries to eat a very diet. So give your microbes natural foods that would help them thrive, i e. Not oreos or cocaine, which was in soft

It doesn't act on a particular receptor the way that like I was describing aceetylcholine and nicotine. It like sort of cozies up to the receptor and it's like soft influence,

Alcohol has anyone that.

Has been drunk, like you know, it affects your motor control and your muscles as well, so it has more than just brain brain effects. But in the brain it acts in that allisteric sort of soft soft power kind kind of a way, and.

Does it kind of mess with frontal cortex activity, Like does it in terms of like loss of inhibition and maybe less control over emotion?

Yeah, it it disinhibits the inhibitory neurons.

Okay, that right.

It's like the act of alcohol is a double negative. Okay, So it works on your inhibitory neurons.

Oh okay, that's why I won't. So they're normally like on like I'm inhibiting and I'm doing my job and then I'll calls like take a break, no gap, Crystal says. The alcohol affects dopamine. Sarah toonin gabba, which is a neurotransmitter that helps maintain calm and glutamate pathways which affect memory. But just as your college roommate may have just lived for Friday Jaeger shots and you have never finished a beer, different people have different genetics that influence how receptors respond

Magical things are like it's if one aspect of the orchestra went completely like we came on steroids. If you showed up and there was like thirty seven cellos and like four of all of the other instruments, whatever, that would sound like that's kind of what recreational drugs do.

Your whole reality is just a picture that your brain has painted based on what it's sensing. How weird is that? What is even real?

And so when the predictions of the brain, or the way that the system that is the brain tries to anticipate or interpret these completely out of whack situation, that's when we get the fun that is recreational drugs.

What happens with psychedelics is it a particular neurotransmitter that is just going off.

A lot of them are acting on the serotonin system. Okay, because serotonin is like when it's sort of a mod it's a modulation. It's more global than a lot of the other neurotransmitters, I would say. And so when you get like a bunch of serotonin like dumped into the system, you have a lot of different brain regions that are all like trying to cope with life.

Is that why people will take supplements like five htp after they will do like Mollie or something like that.

Yeah, you can deplete the amount because your brain is synthesizing those molecules.

There's a limited number of them.

If you think about a factory production line, it only goes so fast, so you can only produce so many toys or so many cars, or you can only produce so many molecules of your particular neurotransmitter.

And so if you have.

Taken Mollie or one of these recreational drugs that has dumped a whole bunch of neurotransmitter into your brain and you've been like backstroking through those happy molecules.

For a while, Oh the water is great.

And when there's time for your brain to go back to normal because it's no longer getting those signals, there's like it has nothing left to give, literally, and so giving it some precursors for the molecules that it needs to replenish. Is sort of a way of helping it get back to normal because you're skipping a few steps in the assembly line.

Got it, so you're not left like high and dry, like literally high and actually dry of the good range juices. Now, this next topic was on the minds of Patron's John Rokevic Graham Tattersall, Maria Generic, Nikki, Sidney Manzil, don Ewald, first time mindfulness question asker Jennifer Ran and first time question asker Ashley Beatty, who wondered about the impact of meditation on anxiety and depression specifically. And now, what about meditation, yoga,

I'm one of those people that is, like, why would you pay your gym membership if you could just go outside and run?

And then I just stay inside what's netflix the entire time?

And that's kind of how I feel about like about mindfulness, Like it's something that you can do quite easily. You know that there's positive effects, Like there's been scientific papers that have shown that there are positive effects of meditation practice, of mindfulness practice that really does help quiet some of the overactivity and the amygdala that we see and like stern society for instance, So why not do it?

I don't do it. I probably should. It would definitely help me a lot. So do as I say, not as I do. Okay, doctor, Yeah, okay? What is your least favorite thing about neuroscience? About brains or about your life as a doctor brain? Essentially on TV and all over the world.

Neuroscience is really hard to do without actually touching the tissue that you're trying to study, and so we use a lot of model brains in order to learn the things that we learn, which is really challenging because a lot of the even the information that I was sharing with you today, like we know this to be true for mice and rats, and we assume that it is also true for humans to the best of our possible ability. But as far as I know, we aren't able to

Right, would you ever donate your brain to science? Who? What do you think I think I would be? I would be a terrible test well subject, like I'm I'm always in.

The outlier, Like I never feel that I am a good representation of the mathematical average of a human anything, So I feel like my brain would give like wrong data or like not accurate data. And I think that actually speaks to There was an earlier question about like why don't we know how these things work? And it's like, well, we can know things pretty accurately for a particular breed of mouse or particular breed of rat because they're all

Isn't it kind of crazy that we just have clones, like animal clones run around? Is that kind of weird? Does that ever creep you out?

It doesn't really creep me out, But I guess because I mostly work with bacteria and with mice and they're not it's easy to not see them as necessarily having personalities.

Yeah, I guess, but I never raised mice.

I was the beneficiary of people that did mouse experiments, but I never actually had a colony of mice that I was raising. And I know that neuroscientists that do work directly with life behaving animals would absolutely tell me that I'm crazy. But they have personalities and differences even though genetically they're the same. Wow.

Do you hear that Barbostressing cloned her dog and she thought she was getting one, and they're like, well, we have four, and she's like fuck, She'd just like, oh no, she'd like give it away to her assistant's daughter or something. She's like, I didn't. I didn't think i'd give four of them. It's true. Barbara Streis and missed her dog, Samantha so much that she had four more made from a swab of her cheek. Now, the runt of that letter sadly died, but she kept two of the other

I mean, I think that we are inherently selfish and that we really like to know things about ourselfs and neurosciences is kind of like my way of trying to understand this like human condition. So, you know, brains are they're really intense, and they want everything to have meaning, and they will subscribe meaning to things that really they're is no purpose too, And so I think that's probably just like what I'm trying to do with my meaningless life is to figure out, you know, why why humans?

That's the best title for a biography, Why Humans? Why Us? Oh As for neuroscience movies, Crystal says, pretty much none of them get it right, like none, and they all try to make things way too spiritual, and that using only ten percent of your brain is a big, hairy, smelly myth, and that this Scarlet Johansson vehicle Lucy was wall to wallflim flam and agregious. So she thinks writers and directors should just focus on the real neuroscience because it's bananas and it's mysterious enough.

Reality is stranger than fiction, and so let's figure out what's actually going on and how can we tell that story in an epic but accurate way, because it really is enough to blow your mind, right, your actual mind.

Thank you so much, doctor Delaware. Thank you for having me of course. Okay, so now that you are fully enchanted by the knowledge of doctor Brain Crystal Dilworth, you could head to Crystaldilworth dot com for links to her social media and her LinkedIn page. There's a link to that in the show notes of this episode, and special thank you to Caseyhnmer for making sure that she got