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1:00

Oh, hey, this is 2023 Allie here to say

1:02

hello to all the new listeners

1:04

via Radiolab, oh, hey. And

1:06

the good news is, is that this Encore is phenomenal,

1:09

and it's helpful for literally

1:11

every person with a brain. The

1:14

bad news is, is that we're running an Encore because

1:16

I have been in the ER

1:18

two times this week with pneumonia.

1:20

Have you ever gotten pneumonia?

1:22

I have, once this week. It

1:24

sucks. So I'm in bed for

1:26

the week, I'm laid out. I have not been this sick

1:28

in decades, my apologies. But please

1:30

enjoy this stellar episode for the

1:32

first time or for an Encore. It

1:35

has tons of stuff that we both know that you may have

1:37

forgotten. And pass it along to anyone else with

1:39

a brain, okay.

1:40

Oh, hey, it's the lady who keeps

1:42

candles in her wallet because you never know when you're

1:44

gonna be in a pinch and it's gonna be someone's birthday.

1:47

And then you'll be more excited about singing to them

1:49

than they'll be excited about being sung to.

1:51

Allie Ward, back with another episode of

1:54

Ologies.

1:55

Okay, you like brains? Does

1:57

your brain like brains? It probably does. So

2:00

right now, your soft, squishy

2:02

think lump is just hanging

2:04

out in your head. It's thinking about itself.

2:07

How does it work? What's in there? Why

2:09

do I want to eat Cool Whip out of the tub

2:11

with my fingers? And why aren't I more excited

2:14

about folding my laundry? The answer,

2:17

molecular neurobiology. But before

2:19

we splish splash into your mood juices,

2:22

let's take care of some business up top and thank all

2:24

the folks on patreon.com slash ologies

2:26

for being in the club. I'm sure you all support the show

2:29

and you hear what topics I'm working on first and

2:31

you submit your questions for theologists.

2:34

Thanks to everyone wearing Ologies merch from

2:36

ologiesmerch.com. Thanks to everyone

2:39

who forwards an episode to a friend

2:41

or who subscribes on their devices

2:44

and rates and especially reviews because

2:46

you know I read your words and I pick a

2:48

freshie to put on blast. Such as Dusky

2:50

who says, they're falling back in love with

2:53

life and that theologists have shown me

2:55

the light. Okay, molecular neurobiology.

2:57

Let's get into it. Let's break it down. So molecules,

3:00

the word derives from the Latin for

3:02

tiny mass and neuro

3:04

comes from the Greek for sinew

3:07

or cord or penis because

3:09

neurons are elongated. They

3:11

look like strings or cords or

3:14

I guess penises. Biology

3:16

of course, the study of life. So

3:18

molecular neurobiology, the

3:20

study of the tiny masses that

3:23

bring our dick looking brain cells to life.

3:25

I'm just reading facts here. Now this ologist

3:27

got a bachelor's in biochemistry

3:30

at UC San Diego and later a PhD

3:32

in molecular neuroscience at Caltech.

3:35

She's also a dancer, a gymnast, a violinist,

3:38

a TEDx youth speaker, a tech

3:40

strategist, and a TV host for

3:42

Voice of America, Al Jazeera America,

3:45

Seeker, Discovery News, and more.

3:48

She's an if then STEM ambassador

3:50

for the American Association for the Advancement of

3:52

Science

3:52

and Linda Hill Philanthropies. And

3:55

finally, she is appointed a role model

3:57

to other women and girls in science,

3:59

technology.

3:59

engineering and math fields. She also appears

4:02

on segments of the new CBS show Mission

4:04

Unstoppable where she is known

4:06

accurately as Dr. Brain. I've

4:09

known her for five years and have adored

4:11

her since we first sat down and shared

4:13

a basket of sweet potato fries in 2014

4:16

and I was just straight-up giddy to

4:18

have her on my couch and to ask her

4:20

one million questions about what

4:22

a brain is made of in white matter

4:25

and gray matter and what makes us happy and

4:27

how do antidepressants work and why are some

4:29

substances addictive? What happens

4:31

on drugs and can I have new habits

4:34

and what is anxiety all about and how depression

4:36

works and caffeine hacks that

4:37

may not work? So get ready to

4:40

fill your ears and the thing between

4:42

your ears with all kinds of wisdom from

4:44

wonderful person, neuroscientist,

4:47

your new good friend, and molecular

4:49

neurobiologist Dr. Crystal

4:52

Dilworth.

4:58

Start recording. Can you

5:00

say your first and

5:02

last name please? I pronounce

5:04

it right.

5:11

Crystal

5:17

Dilworth? I know. Do you want me to spell it for you?

5:19

No! Okay. Dr. Dilworth.

5:22

Dr. Dilworth. I

5:24

always like to ask this question. What was it like when you

5:27

like came out of the room from defending and you're like, I'm

5:29

Dr. Dilworth. So

5:30

I came out of the

5:33

room and my committee was still in there

5:36

and deliberating and normally

5:38

that is one of the scariest moments

5:41

in anyone's life because you're not sure what

5:43

they're going to say but I was I

5:45

was pretty sure because

5:47

my committee chair had been like we're just gonna chat

5:49

for a little bit we'll be right out. They came out and they

5:51

shook my hand and they said congratulations Dr. Dilworth

5:54

and I got an entirely new lease on life.

5:56

Oh my god, I'm so excited.

5:59

Like everything.

5:59

change. Did you know

6:02

growing up that you were gonna be a doctor

6:05

or a neuroscientist? I mean, you

6:07

are really good at a lot of things and I think that

6:09

that sometimes is difficult. No, I

6:12

was gonna be a dancer. I was gonna

6:14

be on stage at Lincoln Center just like all

6:16

of the books that I had read about how to be

6:19

a professional ballet dancer had nothing

6:21

to do with science really. And then so

6:24

were you studying ballet

6:27

and then sneaking into chem classes?

6:29

How did it work?

6:29

Who were you cheating on? Scholastically.

6:33

I think the decision to go to grad school,

6:36

I was definitely cheating on my dance classes.

6:38

I was in professional dance school in New York City

6:40

doing the things that you have to do to be a professional

6:43

dancer and I just wasn't fulfilled

6:45

by the experience. I think it's really hard. I was lying about

6:48

my age so that I could be in the school

6:50

to begin with and dancers

6:52

are they're treated like empty

6:54

vessels, right? The choreographer, the

6:57

artistic director, these are the people

7:00

that are filling the empty vessel with the intention.

7:02

And when you have a bachelor's degree in biochemistry

7:06

and you're used to doing independent research

7:09

as an intern in a research lab, being

7:12

treated like you have nothing personally to contribute

7:14

is very difficult. Yeah. And I was

7:17

looking for an opportunity to

7:19

be an adult and to be treated like I had something

7:21

to intellectually contribute. I wasn't getting that

7:23

in my artistic life. So I

7:26

started skipping my classes and

7:28

taking the subway uptown to Columbia

7:31

and attending the chemistry department lectures,

7:33

which is insane. Now that I

7:36

look back on it, now like nobody goes to those lectures voluntarily.

7:38

Like the grad students are only there because of the free

7:40

pizza, but I was actually

7:42

there for the intellectual stimulation,

7:45

which is terrifying and awful. Wait,

7:47

they give pizza out of these things? Otherwise,

7:49

nobody goes.

7:52

Yeah. Most of those, like weekly

7:54

lectures are accompanied by some type of bribe.

7:57

So why neuroscience? Well,

7:59

Well, I guess I was

8:02

always interested in people and

8:04

their behavior because maybe

8:07

as a homeschooled kid that didn't

8:09

have like a really diverse

8:11

social network. I mean, I had

8:13

a social network, but not the diversity

8:15

that you wouldn't see in like public school

8:18

for instance. Some people's

8:20

their behavior seemed unfathomable to me.

8:22

Like, I just don't understand. Like what is this

8:24

programming and how does it work? And

8:26

so I thought, oh, maybe I would study history.

8:29

Maybe I would study sociology or psychology.

8:33

And my dad said, no. He

8:35

was like, that's not a real science.

8:38

None of those are real sciences and

8:40

you have to choose a real science. What

8:43

was your dad? Did your dad study science? Yeah, his

8:45

background is in physics. My mom's background

8:47

is in microbiology. That was what they

8:49

understood. Okay. Um, and

8:52

I don't think they were afraid of all the things the parents

8:54

are afraid of like, she's never going to get a job. She's

8:57

going to be destitute. She's going to move back home. I live with

8:59

my mom right now, by the way. So

9:03

FYI, best laid plans of

9:05

my sin men. Yes,

9:08

but you're like an international traveler and you're

9:10

like about to move to Sumatra. It's

9:13

true. Yeah. There

9:15

are reasons also that I decided

9:17

to move in with my mother to help take care of her

9:19

as well. But, um, you know, like

9:22

I said, this is their plan. Um,

9:25

but so brains, like, do you start with

9:27

molecular biology? When you decide,

9:30

okay, I want to figure out how this weird big lump

9:32

of stuff in my bone bowl

9:35

in my head works, like, where do you

9:37

even begin with that? You start with like neural anatomy.

9:40

Do you start with chemistry of it? Like

9:42

for me, the Eureka moment was

9:44

I was taking organic chemistry because,

9:46

you know, typical freshmen, O chem,

9:49

what everybody has steak. And I was also taking

9:52

biopsychology, which is the closest I

9:54

could get to a psych class and still like

9:56

have this be approved. Um,

9:59

and I should. I can't

10:00

like clarify that I started

10:03

college really young. So I was probably 14

10:06

or 15 at this time. So

10:08

my parents were still approving my course

10:11

load. So I was restricted in what

10:13

courses I could take based on their approval.

10:16

Oh my God. Wait, I've known you for four years and I

10:18

did not know that you started college at 14 or 15.

10:21

Yeah. What? Yeah.

10:24

I started at a junior college, which, you know, your first two years

10:26

are the types of courses you're able to take

10:28

there. And I transferred to a four year college

10:31

much later. Oh my God. I don't

10:33

think I was wearing a bra at 14. I

10:36

wasn't either. Your parents

10:38

would have obviously like help you figure out what courses

10:40

you're going to take. So bio psychology.

10:43

Yeah, it's kind of backfired because I was in bio psych

10:45

and they laid out in

10:48

the book and in the lecture the pictures

10:51

of the different neurotransmitters, the

10:53

chemicals in our brain that sort

10:55

of determine the brain functionality that translates

10:58

into behavior. And I would just learn

11:00

from my organic chemistry class how to

11:02

identify the critical chemical

11:04

functionalities like that's an oxygen

11:07

group, like an OH group hydroxyl. That's

11:09

a benzene ring and sort of start to understand

11:12

how those things sort of fit with our

11:14

biology. And that was like the aha

11:16

moment. If you're like, quick

11:18

word, what is a benzene ring? It's

11:21

not an oil gang, but more elementally

11:23

it's six carbon atoms that are joined

11:25

in a ring with a hydrogen atom stuck

11:28

to each. And she was like, ah,

11:30

my brain loves this stuff. Now

11:32

her bachelor's in biochem and

11:34

so far most of her college courses were

11:36

more generally about the human body

11:39

chemistry and didn't focus on the

11:41

thinky parts of the human body as much.

11:43

So I didn't really

11:46

go back to focusing on the brain until my

11:49

senior year. So all of my upper division

11:51

electives were in neuroscience and that's

11:53

when I was like, this is how

11:55

I want to apply these things. What?

11:58

Okay. What is the difference between?

12:00

neuroscience, neurology, neurobiology,

12:03

molecular neurobiology. I feel

12:06

like if you don't work with brains, you're like, oh,

12:08

just kind of call it a neuro something

12:10

or other. Like what are those different

12:12

fields mean? Okay, so I'm

12:15

going to take you on a little journey. Okay. Story

12:17

time. I am a first year

12:19

graduate student. I have not yet chosen

12:21

a lab. I am real, I'm at Caltech.

12:24

Every single person that I'm meeting is smarter than

12:26

me. I am incredibly intimidated

12:28

and anxious and like really, really need

12:30

to do a good job. Otherwise I'm going to fail life. And

12:33

I go into my first meeting with the

12:35

professor that's going to be my PhD

12:37

thesis advisor, but I don't know that at the time. And

12:40

I'm trying to impress him with how smart I am. And

12:42

I tell him I'm really interested in

12:45

neurology and I'm really interested

12:47

in brains and the things

12:49

that brains do. And he's like, I'm going to stop you right

12:51

there. I'm going to let you finish. Oh, God. If

12:54

you're interested in neurology, then

12:56

you should be going to medical school. We

12:58

don't do neurology here. Neuroscience

13:01

is the science behind the brain and we

13:03

do research on how the brain works

13:06

and we get PhDs. And

13:09

that's the type of science that we can do on

13:11

the brain here. Are you still interested? Oh

13:13

my God.

13:14

And so that is the difference. I

13:17

would have had immediate reactive

13:19

diarrhea and just excuse myself from

13:22

life. I wouldn't have been like, oops. But

13:24

you know when you're so anxious and your

13:27

whole fight or flight system is engaged and

13:29

you're kind of too numb to it and you're just like,

13:31

okay, take the hit and keep rolling, keep going,

13:33

keep going. There's nothing you can do about it.

13:36

So what is a neurologist exactly?

13:39

Okay, they are physicians, medical

13:41

doctors with MDs, probably

13:43

stethoscopes, I don't know, who treat

13:46

neurological diseases and disorders

13:48

that affect the nerves and spinal cord

13:51

and of course the brain. So you can show

13:53

up in their office and say,

13:54

please doc, fix me. That

13:56

is a neurologist. I honestly don't know

13:58

about this stethoscopes. I just made that up. They

14:01

might not even need them, but you get the general aesthetic.

14:03

And a neuroscientist

14:05

studies the science behind how

14:07

the brain works and why the brain

14:09

works. So you have to have knowledge of some

14:11

of that stuff, but it's

14:13

mostly like hypothesis driven

14:16

investigation. Mm-hmm. Okay,

14:18

so

14:19

a brain. What is it? What

14:22

is this big? Is it mostly fat? What

14:24

is it? Is it proteins? What is it made

14:27

of? Yeah, it's all those good things. All fats and

14:29

proteins and carbohydrates all smushed

14:32

together into a collection of different

14:34

types of cells. There's like 80

14:37

billion neurons and they're all sort

14:39

of smushed together. And there's different

14:41

types of those neurons, those brain cells,

14:43

and they're clustered together in different areas.

14:46

And those different areas have specific

14:49

functions that all have to work together.

14:50

And that's sort

14:53

of what we think of as

14:55

the orchestra of the

14:57

brain as an organ, but that's like not

14:59

even it. But wait, there's more. There's

15:02

like a whole other layer of cells.

15:04

We call them glial cells or astrocytes

15:07

that help those neurons to function.

15:10

So it's not just neurons, but there's like a whole

15:12

other set of support cells.

15:15

And they're not even really support cells because they're doing really important

15:17

stuff. And what do the astrocytes and glial cells do?

15:20

They do so many things. So

15:23

my favorite

15:23

type of support cell is

15:26

the cell that creates myelination

15:28

around electrons. So that's like little

15:31

wire insulators to help the

15:33

electric part of the signal go faster

15:36

down the axon of the neuron. So

15:38

I can like send, if I'm a cell and

15:40

you're a cell, I can send my message to you like way

15:43

faster because of the insulation. And

15:45

that's actually one of the last parts

15:47

of brain maturation. So when

15:49

we talk about brains like not being fully cooked

15:51

until our mid-20s

15:53

and we're still developing, one of the last

15:55

things that happens is

15:57

that installation process goes in.

15:59

in that prefrontal cortex area, which is

16:02

so important for decision making. So

16:04

glial cells are a support cell, and

16:06

glial means glue, because

16:08

it was thought that glial cells just kind

16:10

of held all the neurons together, kind

16:13

of like a bunch of mashed potatoes around a pile

16:15

of yarn. But they do so much more than that,

16:17

and there are different types that do different things.

16:20

We won't go into all of them, but the

16:22

astrocytes are starry shaped,

16:24

hence astro, and they give nutrients

16:27

to neurons, they help repair damage, and

16:29

the oligodendrocytes insulate

16:32

the neurons in the brain by laying down this

16:34

fatty, cozy padding called myelin,

16:37

which is like rubber around an electrical

16:39

cord, or a snuggy that protects

16:41

you from live wires. Now if you have multiple

16:44

sclerosis, like my mom, aka

16:46

our dear Fancy Nancy, who taught you the

16:49

best insomnia hack ever in the Somnology

16:51

episode, the immune system of folks with MS

16:53

likes to eat away at that myelin and cause

16:56

nerve and signaling troubles. Just a side note,

16:58

thank you to all the neuroscientists

16:59

and neurologists working to find a cure for

17:02

MS. We appreciate it, and I want

17:04

to interview you about it please. Now why

17:06

is it important for these diva neurons

17:09

to be so supported and so insulated?

17:12

What do they look like? What do they do? Now

17:14

neurons themselves, those

17:16

are long and have fingers at one

17:19

end, kind of. Can you explain what a neuron

17:21

is? They can be long, they can be short, but

17:23

the critical parts of the neuron are

17:26

the cell body, which is where all

17:28

the good stuff happens, just like a normal

17:29

cell, and the axon,

17:32

which is sort of like that long wire

17:34

that connects one end to whatever

17:37

other cell it wants to talk

17:39

to. There's projections both from on

17:42

each side of the neuron.

17:45

Those would be considered like dendrites, and

17:47

those dendrites create the connections,

17:50

which we call synapses, that

17:52

are how cells talk to each other.

17:54

So it's like sort of the main parts.

17:57

So neurons, they're a cell with a sometimes-

17:59

long axon to reach out to other cells,

18:02

and little fingery dendrites at the end.

18:04

And you may remember the dendrology

18:06

episode with Casey Clapp about

18:09

trees. So just think of those little branches

18:11

at the end of the neurons, those are dendrites. They

18:13

also kind of look like if a bird had a bunch

18:16

of toes and then those toes had

18:18

toes. That's your brain. Okay, so how

18:20

are all these neurons just chit-chatting, gabbing,

18:23

they're shooting the shit, running the show up there,

18:25

what are they doing? My favorite part of

18:27

neuroscience is the fact that neurons

18:29

use both electricity and chemicals. Oh.

18:33

As like communication. Okay, ooh, tell

18:35

me about this. So the

18:37

really important part of neurons is

18:40

that there's like all of these little gates that

18:42

are like regulating the ions

18:44

flowing in and out of them. And like ions are like

18:46

magnesium, calcium, sodium, these are

18:48

really chlorine, these are really important. And they're

18:50

just like constantly moving back and forth.

18:53

But because all of those ions are charged,

18:55

you get like a little electrical field. From

18:59

each of the different cells. And

19:01

so if I wanted to pass a

19:04

signal to you, it would start

19:06

as an electrical field

19:07

that goes all the way down my axon due

19:09

to opening and closing, opening and closing in the

19:11

ions. But then it gets the end and I can't

19:13

transmit electricity to you because there's a little

19:15

gap. And so what

19:18

does a cell do? The cell is like, okay, crap, we

19:20

have to communicate to the Alli cell. She

19:23

likes serotonin. We're gonna release serotonin

19:26

into this little gap. And so

19:28

that's when the electrical signal gets

19:31

converted into a chemical signal, which

19:34

you can read because you speak the

19:36

serotonin language because you have little

19:38

proteins on the ends of you and

19:41

like the end of your synapse and

19:43

you are catching all of those little serotonin

19:45

molecules and bringing them into you. And

19:48

when there's enough of them, it generates

19:50

another electrical signal that

19:53

you can send. Oh my God, and how

19:55

many cells are doing this

19:58

all the time in our brain lumps?

19:59

So I don't know how many cells

20:02

would be active at a given time because that really depends

20:04

on what we're doing. But if you think there's like 80

20:07

billion neurons and then there's like

20:10

estimate like 100 trillion synapses.

20:13

Oh my God. Because it's not necessarily one

20:16

synapse per or two synapses

20:19

per cell. You can have more

20:21

connections. So this

20:24

is a lot. Yeah. We're talking

20:26

the final number is a shit ton.

20:28

Maybe many zeros. Yeah. Okay.

20:31

And so neurotransmitters. This

20:34

is like a chemical messenger that

20:36

cells are sending to each other. And

20:38

what are the main

20:40

neurotransmitters? I know we hear about dopamine and

20:42

serotonin and maybe norepinephrine. But

20:44

take me through some of the players here. Yeah.

20:47

So I think dopamine is like the media darling

20:50

of the neurotransmitter

20:53

world. You have a lot

20:55

of specific chemicals

20:58

like the three that you mentioned

21:00

that are involved in a lot of behaviors.

21:02

But then there's other types of

21:05

messengers as well. So we have

21:08

small peptides like

21:10

we would say oxytocin, which

21:12

it's not necessarily a formal neurotransmitter

21:15

but it's really critical in modulating

21:17

brain function and behavior for

21:19

instance.

21:21

Oxytocin you may have heard is a neuropeptide,

21:24

not to be confused with Oxycontin, which

21:26

is an opiate. But oxytocin can

21:28

promote bonding and feelings of comfort

21:31

and attachment with partners and members

21:34

of a group or with babies. And

21:36

yes, it does increase when you pet

21:39

a dog, which is why you probably

21:41

would not follow around an unfamiliar

21:43

goose in a park and pick up its poo, but

21:46

you would for your dog and not think twice. Now

21:48

on to more neurotransmitters. We

21:51

use

21:51

acetylcholine a lot. So that's

21:53

a neurotransmitter that I studied

21:55

because of its relation to nicotine,

21:58

which I'm sure we'll get to.

21:59

Acetylcholine is really important because it's like

22:02

the fast acting neurotransmitter

22:04

in the brain. So if you need to get

22:06

a cell to respond right away, acetylcholine

22:08

might be the way to go. And it's so fast acting that it's

22:10

used in the body as well to like help

22:13

with muscle contractions. Oh my God. Is

22:15

it like the text message of neurotransmitters? Yes. Get

22:18

at me. Just send me a text.

22:20

Your phone is blowing up. And so

22:22

acetylcholine, can that do

22:25

more than just make you happy or alert? Is

22:28

that, can that send all kinds of messages to you?

22:30

Yeah, it can. So if you think we

22:32

talked about the brain being groups

22:35

of different types of cells and

22:37

each of those cell groups probably has like different

22:39

layers of cells as well. So the complexity

22:42

in the brain is really, really difficult

22:44

I think to imagine. Each

22:46

of those different functional groups of cells or

22:48

different parts of the brain have connections

22:50

to one,

22:51

if not many, many others.

22:53

And they're all talking to each other. That's why I kind

22:55

of call it the orchestra because they're all

22:57

working together. And if you think about each

23:00

different system, like maybe the string system is

23:02

dopamine system and the brass

23:05

section would be your norepinephrine.

23:08

Everybody sort of is talking to each

23:10

other, but in different languages. And it might be

23:12

that I'm a cell that releases acetylcholine,

23:15

but you don't have any receptors for that. So

23:17

you can't see my signal, but somebody

23:19

else can. Did you use

23:21

that metaphor in your PhD defense? Because

23:23

I think it slaps. You should have. I

23:26

didn't. I don't. The orchestra of

23:28

the brain. I'm sure

23:30

it's not original. I think it's

23:32

pretty good. I'm going to look it up and I'll tell you if anyone else

23:34

has used it. Okay, so other folks

23:37

have used this and it turns out because it's a really

23:39

apt good analogy. Also when

23:41

it comes to working on brains, Crystal

23:44

used data from rodent brains to

23:46

try to extrapolate what was happening

23:48

in human brains, including I

23:50

guess her own.

23:52

Did you ever have any existential crises

23:55

when you were like, my brain is studying brains,

23:58

brains on brains on brains? Does it ever freak you out?

23:59

No, I think there's the

24:02

Carl Sagan quote, like we are the way for

24:04

the universe to know itself. And

24:06

so I think that that's kind of

24:08

how I feel as a neuroscientist.

24:11

Do you ever think about certain

24:14

reactions you have to life or certain like,

24:16

if you're having a down day or an up day, are you ever

24:18

thinking about like your orchestra, like you're like horn

24:21

sections going off right

24:23

now? Absolutely. You

24:25

do? Yeah, of course. Does that help you at all when

24:27

you're relating to other people thinking, okay,

24:29

well, this is not just this person's a jerk or

24:31

maybe this person isn't being sad

24:34

for effect. Like do you think about

24:36

them as like a concert of chemicals ever?

24:38

Yeah, I think obviously I can.

24:41

That's when I'm thinking like rationally thinking

24:44

and using that prefrontal cortex

24:47

to try and compose a logical

24:49

flow around why somebody is behaving

24:52

the way that they are. And

24:54

everyday life, it's usually more

24:57

emotion driven, reactivity

24:59

driven. That's how our brains evolved is to react

25:01

to external stimuli, not necessarily to

25:04

think and problem solve about them as

25:06

the first thing, right? Because you don't want

25:08

to be like, is that a snake? I'm not sure if it's a snake.

25:10

I'm going to keep walking towards it until I'm absolutely

25:13

sure. Ouch. Now I'm dying,

25:15

right? That's not how brains, our

25:18

brains work. So I think when I can

25:20

take a step back and think rationally

25:22

about like, why is this person yelling at me? It

25:26

is helpful, but that's, you know, I'm human

25:28

just like everybody else. And that

25:31

prefrontal cortex, that's right behind

25:33

our forehead. And that's

25:35

the kind of meteor chunk that's evolved

25:37

more recently.

25:38

Yeah, I think that's what

25:40

we'd like to think of as one of the

25:42

differentiating parts of human

25:45

brains versus other animal

25:47

brains. And I want to make a comment about animal brains

25:49

in a second, but it's our ability

25:52

to extrapolate, to use

25:55

logic and reasoning to come up with

25:57

creative solutions to problems.

25:59

to not just react and to think

26:02

about downstream effects. That's what

26:04

the prefrontal cortex helps us do. But

26:07

what I was gonna say, which is

26:09

one of the myth busting things, I was like,

26:11

I'm gonna talk to Allie about neuroscience.

26:14

What do I want people to know about neuroscience? Okay,

26:17

the pop culture reference to the

26:19

lizard brain. Yes, yes, okay, okay,

26:21

okay. Let's debunk this flim

26:23

flam.

26:24

Really bothers me. Okay, I

26:26

was gonna ask about it. Because it's often

26:29

one used incorrectly. Okay. It's

26:32

usually when people say, don't listen to your

26:34

lizard brain. It's just

26:36

lizard brain, baby. I think what they

26:38

mean is, don't listen to

26:40

your limbic system. Okay. Or

26:43

your midbrain or the center

26:45

of your brain in which emotions

26:48

are generated and relevant.

26:52

But I think when that quote, and

26:54

I am blaming Sagan again for this,

26:57

when the Sagan quote of there

26:59

is an alligator brain around which

27:01

everything else is wrapped was put

27:03

out there, he meant something even more

27:06

basal, like your brain stem and the

27:08

parts of the brain that control respiration

27:11

and heartbeat and those

27:13

types of really, really basic biological

27:15

functions. But the fact of the matter is,

27:17

is that lizards and reptiles

27:20

actually have something similar to a cortex.

27:22

They do? Yeah, they do. Nothing

27:25

like the giant white

27:27

matter that we have. It's nothing

27:29

like the big prefrontal cortex

27:32

that you would see in primates, but it's

27:34

something that

27:35

evolves similarly. And when I say evolved,

27:37

I mean, the gestational period.

27:40

And you see very similar wiring

27:43

there. So. Poor lizards.

27:46

They're really getting a bad rap. Oh.

27:48

Also, are alligators even lizards? Back

27:51

in the serology episode, I asked lizard

27:53

expert, Aaron McGee about it. Alligators,

27:56

they are lizards. No. No.

27:59

No.

27:59

I just realized I was like, how big does a lizard

28:02

get? Is an alligator, why isn't an alligator a lizard?

28:04

I'm sorry. I'm

28:06

just not. Just not. So,

28:09

so much horsepucky flim flam debunked

28:11

all at once. So you mentioned white matter and gray matter.

28:15

What is the difference? So white matter

28:17

is all, is basically the wiring. Okay.

28:20

So when you would, you would say

28:22

like, there's a pathway

28:24

between two brain regions

28:27

and that's the white matter. It's the connections

28:30

and gray matter is like more

28:33

the cell bodies and the gooier, the

28:35

gooier

28:35

stuff. Okay. Put it that way.

28:37

Is there a skin on it? Kind of, is there like an apple skin on a brain?

28:40

Not the way that you are describing

28:43

it, but we do have a barrier between

28:45

the brain and the blood

28:48

system that provides the glucose

28:50

and the other nutrients to the brain. And

28:53

that's the blood brain barrier is critically

28:56

important to protecting the brain from

28:58

all the things that we're exposed to. Can

29:01

more things leak through that blood brain barrier than

29:03

we realize? Are we finding that out? Probably.

29:05

We used to think that it was impenetrable. And

29:08

now we know that there's evidence of a lot

29:10

more sort of transmission through

29:12

that barrier than we think.

29:15

But it really does protect us. I mean, think about like

29:18

all of the pharmacologicals that you've ever taken

29:20

in your life and some of them can

29:22

slip through and that's good

29:25

because we need them to regulate our behavior. And

29:27

some of them are kept out by that

29:30

barrier, which is great because they could be potentially

29:32

toxic. Okay, well getting

29:34

back to neurotransporters.

29:35

Oh, no. I wanted

29:38

to ask if you'd ever touched a brain before. So

29:40

I had to get us off course. I have touched a

29:42

human brain. It's

29:44

very delicate. Like you don't want to make

29:46

a lot of really fast, and they're preserved brains.

29:49

I haven't like touched a brain of a person,

29:51

which some neurosurgeons

29:53

have. I cannot speak to what it's like

29:56

to touch a live brain, but one

29:58

that's been preserved and formality.

29:59

to hide. It's very delicate.

30:02

It is as gooey as

30:04

you think.

30:06

When you're holding it, if you're anything like

30:08

me, there's an oppressive sense

30:10

of responsibility that

30:13

happens when you're thinking about the life that

30:15

that brain was really responsible for guiding.

30:18

I don't hold it for very

30:20

long. I held it and

30:22

I felt the profound

30:24

nature of what I was doing and then I gave

30:27

it back to the technician. What

30:29

was the setting here?

30:29

What was the setting? Yeah.

30:33

Honestly, this was in undergrad at a science

30:35

fair. And

30:37

that was just one of the really cool exhibits.

30:40

Like there was mouse brains and a

30:42

human brain and you know, like other

30:44

brains that you could just kind of like touch and play

30:46

with. Wouldn't it be crazy if you donated your brain to

30:48

science and they're like, you're just gonna go to science fairs. You're

30:50

gonna recruit some people. You'd be like, okay, sweetie.

30:53

Shake some hands, kiss some babies, not

30:55

shake some babies and kiss them hands. I almost said that

30:57

backwards. Okay, so neurotransmitters,

31:01

serotonin, dopamine. What

31:04

do they do? Do they have different roles in

31:06

terms of our emotions? They have very, very different

31:09

roles. Dopamine, I'm going to start

31:11

with because this is everybody loves

31:13

a good dopamine story.

31:15

I love it. And

31:17

without dopamine, we really wouldn't be motivated

31:20

to do anything. So it's really interesting

31:23

in computer science when they talk about computers

31:26

having rewards so that you can teach it

31:28

like artificial intelligence system

31:30

that

31:31

you're on the right track, keep going.

31:35

We have similar rewards. You're on the right

31:37

track, keep going. And dopamine

31:39

is how our brains have been

31:41

evolved to receive this reward.

31:44

So it makes us feel happy,

31:46

but not really happy. More just like

31:48

pleasure, like things are good.

31:50

And anything that you would do that

31:53

would keep you alive elicits a dopamine

31:56

response. So eating,

31:58

drinking, sleeping. and hanging

32:00

out with your friends, anything that you might enjoy,

32:03

you get a little bit

32:05

of a dopamine hit. So

32:07

it's basically to keep us doing things that

32:09

are going to keep the human race

32:12

alive. Okay. Basically.

32:14

Whereas serotonin is more nuanced.

32:17

It's not just pleasure, but it's mood

32:20

and it's sleep. And it's

32:23

really helping to modulate the way

32:25

that those little dopamine hits are interpreted

32:28

by the larger orchestra. If

32:31

that makes sense. Yeah. And

32:33

what happens when

32:34

they get off? Is there not enough

32:36

to send a signal to the next neuron?

32:39

Is there too much? And

32:41

why does it seem like

32:43

a very slim percentage of people have

32:46

a good balance? I feel like, or maybe

32:48

it's just living in LA or internet

32:51

culture, but I feel like everyone's

32:53

like, oh yeah, my neurotransmitters

32:56

are whack. I'm no minor. So I

32:58

mean, unfortunately I want,

33:01

I want to respond to you philosophically.

33:04

Like

33:06

when we first sequenced the human

33:08

genome, the lead researcher

33:11

on that project was the genome that

33:13

they chose to sequence. Does that mean

33:15

that he's the most normal genome

33:18

and every other genome is going to be compared

33:20

to his maybe it

33:22

was an arbitrary center for

33:24

science to pick. Right?

33:26

Okay. So quick aside, there was the publicly

33:29

funded human genome project and the

33:31

first public genome came mostly

33:33

from a single anonymous male donor.

33:36

I think this would be a sperm donor from

33:39

Buffalo, New York, but then aside

33:41

privately funded genome research

33:43

project was launched by geneticist J.

33:46

Craig Venter, who later admitted

33:48

that his DNA was among

33:50

the first donor pool to be fully sequenced,

33:53

tossing his own genetics into a research

33:55

project was

33:56

later addressed in the journal science

33:58

in an article bearing the

35:59

except for sleep. So

36:01

they just didn't do anything. But like, people

36:03

have probably experienced this before. Like

36:06

you're in a really good early stage

36:08

of your relationship. You don't

36:10

eat, you like your sleep's kind of disrupted.

36:13

All you want to do is like read your text messages

36:16

over and over and over again, or check

36:18

your phone to see if you've got another one. Your normal

36:20

function is disrupted because you've

36:23

got dopamine floating

36:25

around in there at levels that you're totally not used

36:27

to. And there's probably some oxytocin in there

36:29

as well, like really fucking things

36:32

up. Oh my God. Wait. So then

36:34

at what point does that decline?

36:36

Is

36:36

that like the two year period of like,

36:39

I'm over this. Yeah, I think we get,

36:41

we get used to it. Yeah. Right. And

36:43

then we can sort of like mellow out and

36:45

become more normal. Um,

36:48

the rats, some of them died because they

36:50

didn't, they didn't eat or

36:52

really do anything because they were just

36:54

super happy pressing

36:56

that lever for their dopamine

36:58

hit. So don't do that. Just pathologically

37:01

fulfilled. Oh no. Okay. Side

37:04

note. I read one article that estimated

37:06

four years was when dopamine starts

37:09

to wane, but

37:10

I really should ask a psychoneuroendocrinologist

37:12

or perhaps a biological anthropologist

37:15

about it. But if things are starting

37:17

to feel a little

37:18

stale with a partner, some

37:20

researchers think that doing scary

37:22

or novel things together, like,

37:24

I don't know, zip lining or going

37:27

to haunted houses or Costco

37:29

on a Saturday, those things can

37:31

get those new romance brain juices

37:34

squirting again. Okay. What happens if

37:36

you don't have enough dopamine? If you don't have enough

37:38

dopamine, it depends on what

37:42

parts of your system are disrupted.

37:45

But

37:45

most of the classical symptoms

37:48

that we see for like ADHD

37:51

or depression or, you know, even anxiety

37:53

and in some cases usually

37:56

have to do with disruption of the dopamine system. That's why

37:58

it gets all the media attention. The classic

38:00

depression is lower levels of

38:03

dopamine, which means that you're

38:05

just not having the same response

38:08

that someone that doesn't have depression to your

38:10

dog or to normal

38:14

things in your life that would normally make you

38:16

happy. You're tired, you're lethargic,

38:19

there's a lack of motivation and

38:21

you just aren't getting pleasure from the task

38:24

that you normally would. So it's like

38:26

that grayness, that lack of

38:29

color,

38:29

everything sort of seems blah. That

38:32

would be what it would be like to not have enough

38:34

dopamine in your system. And is that

38:37

because the dopamine

38:39

isn't being produced at high enough levels

38:41

or it's just like not making the jump between

38:43

the neurons?

38:46

That's something that is sort of on

38:48

an individual basis, but I would say

38:50

overall, it's probably your system

38:53

isn't able to produce enough dopamine.

38:56

So there's all these little packages of

38:58

the dopamine chemicals that are sitting at the

39:00

terminals like near the synapse, like just

39:02

ready for the signal, like release us, we're

39:05

ready to go. All systems are go. And

39:07

someone that has lower numbers

39:09

of those little vesicles, those little dopamine

39:12

packets, like even if the cell was like, okay,

39:14

go release all the dopamine

39:16

that you have, is going to be a lower

39:18

level, less packages of

39:20

dopamine released than

39:23

what we would consider to be a normal

39:25

cell. And then what about serotonin

39:28

then? Does

39:31

serotonin play a big part in depression

39:33

and anxiety and ADHD as well? Yes.

39:36

And all of the other things that all of us have?

39:39

The problem with the orchestra is that you

39:41

can't just remove one section, right?

39:47

Like they all work together. So yes,

39:49

they're definitely, serotonin is definitely implicated

39:52

in

39:53

pretty much

39:54

like everything. You know, our predefine is implicated

39:56

in pretty much everything, but it's just a matter of like, what

39:59

is the major contribution?

39:59

So

40:01

serotonin and depression, we're

40:04

used to thinking about SSRIs,

40:07

which are selective serotonin reuptake

40:09

inhibitors, which that's

40:12

the medication that we are giving

40:14

to people with depression. And

40:16

why is that? We want more

40:18

serotonin to be floating around

40:21

in that synapse, in that space between the

40:23

two cells. We want it to be sitting around

40:25

longer. So that signal to

40:28

continue elevating your mood is a

40:30

bigger signal. So there's usually

40:31

these little Pac-Mans that live

40:34

in that space between the two cells that

40:36

collect all of the leftover molecules

40:38

and bring them back into the cell. Like,

40:40

okay, we don't need you anymore, so you're

40:42

going to come and live back in the cell again. And

40:45

if we inhibit those little Pac-Man

40:47

collectors, then we get

40:49

more chemical in that synapse.

40:52

And that

40:53

raises the probability that the

40:55

next cell is going to have a prolonged

40:57

signal from that neurotransmitter.

41:00

Okay, so by cock-blocking the

41:02

neurotransmitter gobblers, there

41:04

will be more in the spaces between the neurons

41:07

to deliver messages. Kind of like if you canceled

41:10

a neurotransmitter's lift and you

41:12

just kept him at the party longer. You're like, sorry,

41:15

what can I say? We love having you around. You're

41:17

great at conversation. We love the signals

41:19

you send. This is a question that I

41:22

have had for years, but I feel like I read somewhere

41:24

that neuroscientists don't really

41:27

know how antidepressants work. Yeah,

41:29

no. Is that true? There's

41:32

so many medications and like, I'm

41:34

sorry, big pharma. There's so many

41:36

medications that we don't actually understand

41:39

the molecular mechanism for, but if

41:41

it works and the side effects aren't too

41:43

bad, we're just like, just

41:45

put it out there and it'll help people. Oh

41:47

my God. Okay, so we don't totally

41:50

know how SSRIs work.

41:52

We just know that a certain percentage

41:55

of people when they take them are like, feeling

41:57

better. We know exactly

41:59

how. they work. We

42:02

don't know why they work. Like

42:05

we don't know why keeping

42:07

the serotonin or the norepinephrine

42:10

or the dopamine around in

42:12

the synapse and increasing

42:15

the signal leads to the behavioral

42:17

changes because the level of complex,

42:20

we can ask those molecular questions. Like that's

42:22

the level I like to look at because it's a lot more concrete.

42:25

We can get answers there, but the

42:27

multiple layers of complexity from like, well,

42:29

which cells

42:29

are getting the attenuated signal and

42:32

what brain regions are those cells in? Oh,

42:34

but it's this brain region, but it's only those brain layers

42:38

of that brain region. And

42:40

what are those particular

42:42

active regions doing

42:44

when they're working in concert? And

42:47

how does that map to the genetic

42:49

background of this individual and

42:52

the external stimulus? And why does

42:54

that mean that giving this SSRI four

42:56

weeks later, this person is willing to get off their couch?

42:59

We don't know. Yeah. I always wondered about the lag

43:01

time there because that is the toughest. And

43:03

I know that this is like a psychopharmacology

43:06

question, but that is the toughest. If it's like,

43:08

hey, you're depressed, take this thing,

43:10

man, six weeks, there's

43:12

a 20% chance you might feel better. Like

43:14

you could have a lot of faith and lucky for me,

43:17

like, you know, well, not lucky for me, but I tried

43:19

a few different medications for anxiety and depression

43:21

before I found one that worked. I've mentioned this

43:23

in another episode, but I tried a genetic

43:26

test to see which anti-anxiety or

43:28

antidepressants would work better for

43:30

me. And I ended up going with something

43:33

that was recommended. It was an SNRI, but

43:35

you should do your own research. I did a ton

43:37

of reading and I decided I didn't have much to lose.

43:40

And I tried a company called GeneSight, which has

43:42

a sliding scale. It's super affordable. They are

43:44

not a sponsor, but it helped me out. But

43:46

your mileage definitely may vary. Anyway,

43:48

let's move on to Crystal's research

43:50

on nicotine addiction. And what did

43:53

you learn about how addiction works

43:55

having studied

43:56

the mechanisms behind nicotine?

43:59

For nicotine, it's super crazy. When

44:03

you're exposing yourself to nicotine, you're actually

44:05

changing the way that proteins

44:07

in your brain are expressing. So

44:10

they're like, oh, cool.

44:12

I really like this. I would like it

44:14

again. I would like it in a specific way. So

44:16

I'm going to change the way that I'm making the proteins

44:19

in my cells so that they are

44:22

better able to bind and

44:24

respond to this drug that

44:26

I have now been exposed to and know exists in the

44:28

world. And so what does nicotine do? Does

44:31

it wedge itself where a

44:33

different neurotransmitter should be? Yeah.

44:36

So nicotine looks a lot like acetylcholine.

44:39

So the receptors that bind nicotine

44:42

also

44:42

bind acetylcholine. They

44:44

are called nicotinic acetylcholine

44:46

receptors. Of course they are. They like dominated my

44:49

life for five years. But

44:52

what looks similar to a protein might

44:54

not actually look similar to us.

44:57

So acetylcholine is the one that's responsible

44:59

for those muscular contractions. It's

45:02

super fast acting. Scientists

45:04

also think it may affect memory and attention.

45:07

And crystal produced from her purse two

45:10

molecular models, as one does. So

45:12

she showed me that nicotine is a double

45:15

ringed molecule with two nitrogens. And

45:17

acetylcholine has one nitrogen

45:20

that's crowded with methyl groups, which

45:22

are three hydrogens bonded to a carbon.

45:24

But in a nutshell, crystal describes both

45:27

molecules

45:27

as having similar friends, aka carbon

45:29

atoms, that give them kind of an analogous

45:32

bulk when it comes to fitting into the

45:34

same receptors. So they look

45:36

similar enough to the receptor that

45:38

it responds in the same way. Got it. So

45:41

it's like when you're doing a puzzle and you find a piece that doesn't quite fit, but you

45:43

can jam it in and then it fucks everything else up? Pretty

45:46

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

45:48

that. That's exactly what's happening. And

45:51

so how do some people who might

45:53

be, say, predisposed to that

45:55

kind of addiction, how do

45:57

they have a better chance at beating

45:59

it? they want to if they're like, I'm

46:02

done with you vaping. I'm done with you like

46:05

cigarettes. Like what do they do? Well, beating

46:08

addiction is really challenging because

46:10

you have like a learning and memory component. And

46:12

then you have a chemical dependence component,

46:14

especially for smoking because

46:16

you'll be like, oh, I'm done. I

46:19

don't smoke anymore. I'm

46:21

successful. And then you'll have one

46:23

drink too many. And suddenly

46:25

you've got a cigarette in your hand and you're not exactly sure

46:28

why. And there's a chemical reason for that.

46:30

But there's also a learning and memory component.

46:32

Like you definitely beat your

46:34

addiction to smoking at work

46:36

and at home. You did not beat the addiction to smoking

46:39

at the club. In the club, we are all family.

46:41

Because you've learned that

46:44

you have three drinks, then you go outside and you have a smoke.

46:47

So it's those behaviors that

46:49

can really hang

46:51

up recovery. Nicotine is actually one of

46:53

the most addictive substances. So

46:57

I was listening to the addictionology

47:00

episode that you did. And

47:02

yeah, there's a lot of really, really terrible

47:04

withdrawal symptoms. Like withdrawing from alcohol

47:07

is potentially lethal. So you need to be careful.

47:09

We've seen media depictions of withdrawal

47:12

from heroin, for instance, which

47:14

looks like it's the one where everyone's like, oh

47:16

my god, I'm being attacked by bugs and my skin

47:18

is itchy. And I need to get my skin off. Like that's

47:21

awful. You're not going to get that if you try and quit smoking.

47:24

But once you go through those really,

47:26

really awful terrible withdrawal periods,

47:29

you have a really good chance of not

47:31

doing those drugs again. Whereas with nicotine,

47:34

it can come back really at any time. OK,

47:37

so what can one do? Is

47:39

there any promise when it comes to

47:42

meditation and mindfulness and breathing

47:44

exercise? Can you retrain your brain

47:46

through healthier behaviors at all?

47:49

Yeah, you can definitely retrain your brain. You

47:52

can also, through meditation, mindfulness,

47:55

and cognitive behavioral therapy, reduce

47:58

the reason that you're smoking.

47:59

at all. So we see smoking

48:02

behaviors, especially with addicts,

48:05

but yeah, like people that are addicted

48:08

to nicotine, oftentimes

48:11

are in response to other things. So schizophrenics

48:14

have a very specific smoking behavior.

48:16

We think they're trying to self-medicate veterans

48:18

come back, not even with PTSD, but just that

48:20

have come back from really traumatic experiences.

48:23

Possibly they're smoking in the

48:26

characteristic way that they smoke to reduce

48:28

activity in their amygdala.

48:29

So you may remember

48:32

the amygdala from the two-part pharaology

48:35

episode, and it is a little brain nugget that

48:37

I like to think of as the screaming

48:39

almond of terror.

48:43

So some folks may self-administer

48:45

nicotine to appease their shrieking

48:48

almond. Does it solve problems? No, not

48:50

at all. It only makes worse. Blame your almonds

48:53

and then try to outsmart it. There's

48:55

lots of different

48:58

indications that could cause somebody to

49:00

smoke heavily that would make quitting harder.

49:04

Is that at all the same when it comes

49:06

to anxiety or depression or ADHD?

49:08

Are there any kind of situational

49:11

triggers that might affect our levels of neurotransmitter?

49:14

Yeah, that's a problem. So we have that

49:16

learning and memory, as I was saying, component.

49:19

So we've learned something is dangerous

49:21

to us, even if it's not, then

49:24

our bodies are going to continue to respond to it that way.

49:26

And you have to retrain.

49:28

No, that's not like some people

49:30

are scared of dogs. Some people are scared

49:32

of people. You

49:35

are snakes. My mom

49:37

is terrified of snakes. And

49:40

it was my brother-in-law and he is like a six

49:42

foot four heavy metal guitarist with hair down to his

49:44

waist. And he can't if he sees a snake

49:46

on TV, he's like, turn it off. Yep.

49:48

My mom is exactly the same way. She gets like the

49:50

chills because and then she

49:52

like runs out of she runs out of the room. And

49:55

so if she decided that was something that

49:57

she wanted

49:58

to learn to not be afraid of,

49:59

afraid of, there are ways through

50:02

like overexposure and other therapeutic

50:05

methods that I don't know anything about, but I know exist

50:08

to

50:10

rewire the brain. Probably

50:12

that direct signal of snake

50:16

fear is never going to really go away,

50:18

but you might be able to add a layer of regulation

50:21

like snake checkpoint.

50:24

Okay, I'm going to react in a different way

50:26

instead of I'm going to react with my

50:29

fear response. And will your neurons

50:31

form new pathways? Will they kind

50:33

of make new channels? You are referring

50:35

to neuroplasticity. I did it. Yes, you

50:37

did. Yeah, you

50:40

can definitely create new connections.

50:43

We're doing that all the time. If we couldn't do

50:45

that, we wouldn't be able to learn anything new and we

50:48

wouldn't be able to teach babies all the things that they need

50:50

to learn in order to be competent humans.

50:52

I mean, I've got to assume that there's some

50:54

of those out there. So

50:57

yes, through using particular

51:00

pathways, particular connections in the brain,

51:02

you can make those connections stronger. You can

51:04

recruit other connections to

51:06

make that pathway larger. I like

51:08

to think of it as like you start out with like a hiking

51:11

trail that you were told was a trail

51:13

and Google maps doesn't really have it on

51:15

there and you have need a machete and you're kind of like

51:17

hacking through it. It's a jungle in here.

51:20

But if you walk that trail many, many

51:22

times, it eventually becomes much easier

51:24

to use and it can

51:26

eventually become like a six lane

51:29

super highway. That's very, very fast

51:31

to go down. And that's the preferred method because our brains

51:33

are really lazy. They don't want to do

51:35

new things. They don't want to think about

51:37

anything. They just want to react because that's how we

51:40

stay alive. And so if you can train

51:42

your brain that taking the path that you

51:45

want it to take is actually easiest and

51:47

allows it to be the most lazy, then

51:49

you can influence the path that it chooses to

51:52

take without you cognitively having to control

51:54

it all the time. So practice

51:56

makes a habit kind of. Yes. Well,

51:59

that's good to know.

51:59

I have a gym membership that I have not used

52:02

in a month and I'm like, okay, can

52:04

I ask you questions

52:07

from patrons? Yeah. Okay. Now,

52:10

before we dive into the questions that you submitted on Patreon,

52:12

a few words about sponsors who make it possible

52:14

for Ologies to donate to a different cause each

52:17

week. Now Crystal is once again an if

52:19

then STEM ambassador for the Lida Hill

52:21

Foundation, which works with a few nonprofits. So

52:23

that's already amazing. But she chose

52:25

her donation to go to the Gina Davis Institute

52:28

on Gender and Media, founded by

52:29

Gina Davis, who has said,

52:32

what our children see sets the framework

52:34

for what they believe is possible. So

52:37

the Gina Davis Institute on Gender and Media

52:39

is the only research-based organization working

52:42

from within the entertainment industry to

52:44

improve gender balance, to reduce stereotyping,

52:46

and to create diverse female characters

52:49

in entertainment and media for kids 11 and

52:51

under. So thanks, Dr. Dilworth. A

52:53

donation will go to them and that is made possible

52:55

by some sponsors of the show, which you may hear about now.

52:59

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53:01

I love them. They are lovely. Listen,

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did I ever think that I would fawn over dishes?

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which is good because I bump into things. They

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53:31

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those mugs and I'm like, you're coming with me, baby. They're

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Also people at East Fork listen to ologies. So

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BarkBox believes in a couple of things.

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57:40

Okay let's get to your molecular neurobiology

57:43

questions shall we? I have questions

57:45

from Petron. And also this definitely

57:47

warrants like a psychopharmacology follow-up

57:50

because absolutely I think that given

57:53

all of the the response to

57:55

and all the questions you definitely need like a psychiatrist.

57:58

Yes!

57:59

This podcast is not intended

58:02

to diagnose or treat. Okay,

58:04

a lot of folks had

58:07

questions about this. Jack, Jennifer Alvarez,

58:09

Elise, Anna Thompson, Grace Lauren,

58:12

Rachel Thompson, Panic,

58:14

or Paynik, either way. Donald

58:17

McGregor, Pandora Two, Rebecca, Lynn Weisselberg,

58:20

Juliana, Aria Sal and Penny

58:22

Lee, and generic Nicky, all asked

58:25

about ADHD. Jack said very,

58:27

very plainly, I have ADHD.

58:30

What exactly is wrong with my neurotransmitters?

58:33

And so yeah, all those folks, and I'm curious about

58:35

it too, because sometimes I'm like, do I have ADHD? Maybe

58:38

I do. I don't know. So classically,

58:40

ADHD is described as a disruption of

58:42

the dopamine system. But I

58:45

think that there's a lot to be said for the

58:47

involvement of other neurotransmitters.

58:50

We like to talk about serotonin, but I actually

58:52

think that norepinephrine is more

58:54

relevant to ADHD specifically,

58:57

because norepinephrine is responsible

59:00

for attention and alertness.

59:03

So when your norepinephrine

59:05

system is working, you're

59:08

awake and you're alert. When

59:10

it's really activated, it's telling

59:12

you there is something you need to pay attention to right

59:14

now and be very awake and maybe run. You

59:17

never know when you may have to jam. And

59:19

so

59:21

the attention needed to perform and

59:23

complete a task

59:24

was associated with norepinephrine

59:27

sort of cycling. So there's

59:29

a lot and then there's not so much and then there's a

59:31

lot and then there's not so much. It's like just

59:33

enough to kind of keep you on

59:35

task and motivated. And

59:37

that motivation also comes from dopamine. But

59:40

when it's tonic, when it's just kind of like

59:42

at an okay level and just kind

59:44

of like plugging along, there's really no

59:47

reason for you to maintain attention

59:49

because it's not telling you to do

59:51

so. And so you're like,

59:53

huh, I want to feel good about something. And

59:55

then when you go looking in search of dopamine because

59:58

dopamine in ADHD.

59:59

people is a little bit lower. And so

1:00:02

they're constantly looking for stimulus

1:00:04

that's going to pop that up so that they can feel

1:00:06

good.

1:00:07

Oh, wow. Why do you think so many people

1:00:09

have ADHD or are getting

1:00:11

diagnosed with it? And I know so many people who

1:00:13

are diagnosed later in life, like, why do you think

1:00:15

it's so prevalent? I don't have

1:00:18

a good answer for that. There's a lot

1:00:20

of discussions people have about

1:00:22

our technology training us to have ADHD, about

1:00:25

the fact that we have declared a thing, kind

1:00:28

of promoting the diagnoses

1:00:31

of it, and not being

1:00:33

able to compare to 20 years ago to know if

1:00:35

it really is increasing in prevalence because

1:00:37

we've just started diagnosing it. This

1:00:39

is an argument that's used for a lot of things.

1:00:42

So I don't really have

1:00:44

a good answer for you. But

1:00:46

I think that it might be that we're just becoming

1:00:49

aware of our differences. And

1:00:51

ADHD is a way for us

1:00:53

to label those differences. Sometimes

1:00:56

that's a good thing. But it isn't

1:00:58

always. I know that there's a lot of really

1:01:00

smart, really, really energetic

1:01:03

and curious kids that get diagnosed with

1:01:06

ADHD. And it might just be because

1:01:08

we have a hard time handling

1:01:10

that level of energy and curiosity.

1:01:13

All right, quick aside here. We ended

1:01:15

up doing a three-part episode

1:01:18

on ADHD with the Russell Barkley.

1:01:21

We did it in 2022.

1:01:21

And people, it's

1:01:23

a banger. It's linked in the show notes.

1:01:26

Wow, changed my life. Also,

1:01:28

though, in 2019, I did look this up.

1:01:30

An adult ADHD diagnosis rose 123% between 2007

1:01:33

and 2016. And

1:01:38

the prevalence of ADHD in kids went up 26%.

1:01:41

So many researchers think it's just awareness

1:01:44

of symptoms that's driving more people to get

1:01:46

evaluated for it. And I know so many

1:01:49

folks with ADHD, some diagnosed

1:01:51

in adulthood that just wish they knew

1:01:53

sooner. I just want to

1:01:55

tell you that

1:01:56

in the process of writing this aside, Jarrett

1:01:58

was typing really loudly.

1:01:59

got his keyboard and I got distracted so

1:02:02

I went and got the headphones that I had lost

1:02:04

for about six months but just found and then in the process

1:02:06

I wandered into the kitchen to make a matcha latte

1:02:09

and then I sat back down but I got an email and

1:02:11

so I ended up checking my credit score for a while. Anyway,

1:02:13

okay, yes, ADHD awareness. It's up.

1:02:16

More people might have it than they realize.

1:02:18

And then what about treatment for ADHD?

1:02:21

I know like amphetamine salts are sometimes

1:02:24

prescribed. What is that doing to the dopamine

1:02:26

or what is that helping

1:02:28

level out? So when I

1:02:31

learned about this, which was a while

1:02:33

ago, we were talking about the

1:02:36

use of amphetamines in the concept of homeostasis.

1:02:39

So our entire system

1:02:41

is designed to keep us in a certain

1:02:44

region of activity and alertness

1:02:46

and awakeness. We want to maintain that

1:02:48

homeostasis

1:02:48

because when we get thrown out of it we get

1:02:50

disease and a lot of terrible things. And

1:02:53

so when you take an ADHD

1:02:56

brain and you give it amphetamine, you're

1:02:58

releasing a lot of norepinephrine, you're releasing

1:03:00

a lot of adrenaline, you're releasing a lot of dopamine

1:03:03

and that's like throwing you way up. So in

1:03:06

a way it's compensating for the things that you might not

1:03:08

have enough of but it's also telling

1:03:10

your body, hey,

1:03:11

as a complete system you better pay

1:03:13

attention to what's happening here because something has

1:03:15

gone crazy and it's forcing your system

1:03:18

to level you out. So

1:03:21

if you don't have those discrepancies

1:03:23

though, the lower level of dopamine,

1:03:26

then you've thrown your entire system into a whole other

1:03:28

solar system

1:03:34

which is for some people good.

1:03:36

That's why we love cocaine because we love

1:03:38

a lot of dopamine and we want that to hang around

1:03:40

for a while but

1:03:41

usually ends up in really,

1:03:43

really bad results. Right. But if you

1:03:46

are already low on

1:03:48

the dopamine then it just levels you off to where

1:03:51

maybe a neurotypical person might be. Oh,

1:03:53

that's fascinating.

1:03:55

So the first line of therapy

1:03:57

for ADHD is usually medication? Why is

1:03:59

that? Well, it works in up

1:04:01

to 80% of folks suffering with ADHD if

1:04:04

the dosage is right. But the best strategy,

1:04:06

doctors say, is combining strategies.

1:04:09

So exercise, some supplements like

1:04:12

fish oil and magnesium have

1:04:14

been shown in some studies to improve symptoms and

1:04:16

being around nature every day can also be effective.

1:04:19

Either way, there is no shame in the ADHD

1:04:21

game. Super common and there are

1:04:23

treatments out there. And yes, I want to do a whole

1:04:25

episode on this. But besides, everyone

1:04:28

wakes up and pours themselves

1:04:29

a piping hot cup of stimulants anyway,

1:04:32

right? But one of the interesting things about homeostasis

1:04:35

is that

1:04:36

it doesn't have to be, like it's something that our body

1:04:39

does naturally and it doesn't necessarily have

1:04:41

to be drug related. Although,

1:04:43

like the, there's a really

1:04:45

great story about homeostasis in coffee.

1:04:49

So if you go through the same morning routine,

1:04:53

when you wake up and you go down, you're about to press

1:04:55

the button on your coffee maker, make maybe

1:04:57

the sound of the coffee maker and the sound of

1:04:59

the coffee going into the pot or the cup. Your

1:05:01

body knows I'm about to get some caffeine.

1:05:04

So we'll depress its system in

1:05:06

anticipation of the stimulation

1:05:09

from caffeine. So that's why like replacing

1:05:12

your coffee with decaf is like

1:05:14

a really terrible trip to play on people

1:05:17

because you'll actually get

1:05:19

more depressed

1:05:22

than you would otherwise

1:05:23

because your body has depressed the system waiting

1:05:25

for the stimulant and then it has not gotten

1:05:27

it.

1:05:29

Fuck. Yeah. So

1:05:31

be really careful with your

1:05:33

routine. Oh my God. I

1:05:35

still say we use the routine we have. Caffeine

1:05:38

binds to the thing that makes you sleepy.

1:05:41

It takes the place. So

1:05:43

caffeine interacts with adenosine receptors

1:05:45

and adenosine receptors are just

1:05:48

kind of like open and waiting for the adenosine

1:05:50

to come and it comes and it binds

1:05:52

them. And if enough adenosine binds

1:05:54

enough of the receptors and it's like,

1:05:56

okay, we're sleepy now. We're

1:05:59

going to go to bed.

1:05:59

But the caffeine comes and it like sits

1:06:02

in that binding site and prevents the

1:06:04

adenosine from binding the receptor but

1:06:06

doesn't activate them. So the

1:06:09

adenosine can't get in and the

1:06:11

receptors like waiting for a signal that never comes.

1:06:13

The caffeine is like, haha, you are awake now

1:06:15

forever.

1:06:18

So yes, caffeine, it swoops in

1:06:20

and it takes the seat of the sleepy chemical,

1:06:22

kind of like musical chairs and it blocks

1:06:25

the snoozy feelings. What if

1:06:27

you are staring at the ceiling and

1:06:29

not even the fancy-nancy trick of

1:06:32

thinking of a category like fruits or cities

1:06:34

or Star Wars characters and then going down the alphabet

1:06:36

thinking of things in that category that start with each letter

1:06:39

is working. Is it best to gradually

1:06:42

taper off caffeine? Like

1:06:46

if you need to. If you needed

1:06:48

to, like why would you stop drinking coffee? I don't

1:06:50

understand the question. She

1:06:52

says with a coffee cup. I don't know.

1:06:55

Why would anyone do that? Okay, a lot of people

1:06:58

had questions about the genetic levels

1:07:00

of neurotransmitters

1:07:00

like Radley, Joe

1:07:03

Portfino, Corey Navis, Kinley Wallace,

1:07:05

Andrea, essentially asked,

1:07:08

you know, anxiety, depression, hereditary,

1:07:11

contagious. Radley asked, are

1:07:13

imbalances in neurotransmitters more likely

1:07:15

due to genetics or environment? Speaking

1:07:18

as someone with a whole slew of mental illnesses

1:07:20

and addictive behaviors in my family, including

1:07:22

myself.

1:07:23

And Radley, you're not alone. I feel like most

1:07:25

of us are probably in the same basket. Going

1:07:28

into Thanksgiving, everybody's going to

1:07:30

know that they're in a family of nuts. Absolutely.

1:07:33

We all are. All of

1:07:35

us. There's so many ways that neurotransmitter

1:07:38

levels can be affected. Definitely

1:07:40

genetics is one of them. Definitely

1:07:43

environment is another. And things that we're

1:07:45

temporarily going through can influence

1:07:47

it as well. So like if you've just

1:07:49

experienced a traumatic loss, you

1:07:52

are going to have differences in your

1:07:55

neurotransmitter release. But

1:07:57

that is temporary and it will eventually go back

1:07:59

to what we're doing. but for you as a normal level and you're

1:08:02

able to cope. But some people

1:08:04

that have genetic differences,

1:08:06

what does that even mean? It could mean we

1:08:09

produce different amounts of neurotransmitter.

1:08:11

It could mean that our receptors have different

1:08:14

responses to those neurotransmitter than

1:08:17

a neurotypical response. There's

1:08:19

so many different ways that the

1:08:21

amount or the reaction

1:08:24

to a neurotransmitter can be

1:08:26

affected by genetics or by environment.

1:08:29

So the answer is yes. Yes. That was a very long

1:08:31

yes answer. So genetics can

1:08:33

influence your neurotransmitter levels, for sure.

1:08:36

But before

1:08:36

you blame your parents for everything,

1:08:39

a whole bunch of factors are also

1:08:41

at play. So it's not you, fancy

1:08:43

Nancy. It's me

1:08:44

or dad or how much caffeine I drink or

1:08:47

maybe jet lag or the fact that I have a minute in the gym

1:08:49

in a month. Anyway, what about

1:08:51

SNRIs versus SSRIs?

1:08:53

I know Aurora, Heather Gentry, Gracie

1:08:56

Zeca, Leanne Shister, Rachel

1:08:59

Polivica, and Amelia H.

1:09:01

All wanted to know, do we know why different

1:09:04

SSRIs and SNRIs have different effects

1:09:06

on people? Amelia H.

1:09:08

wanted to know, is it just the molecular structure?

1:09:10

Heather Gentry is a first time question

1:09:12

asker. So is Gracie Zeca. And

1:09:15

they both kind of asked about increasing

1:09:18

numbers of atypical antidepressants. And

1:09:20

if the serotonin and depression model

1:09:23

is not correct, if it's bigger than

1:09:25

that. It's definitely bigger than that. OK.

1:09:28

It's definitely bigger than that, especially

1:09:31

when you're

1:09:31

talking about the interplay between

1:09:33

depression and anxiety. And

1:09:35

that's what I think of when I think of a combination

1:09:38

of SSRIs and SNRIs.

1:09:42

So

1:09:43

we're still talking about reuptake inhibitors.

1:09:45

We're still talking about the little

1:09:47

molecules that go around collecting the

1:09:49

neurotransmitters and shoving them back into

1:09:51

the cell that they originated from and waiting for the

1:09:53

next opportunity to release them and

1:09:56

inhibiting this process. So keeping those

1:09:59

neurotransmitters.

1:09:59

in the synapse longer so that you get a more

1:10:02

prolonged signal. Now we're talking

1:10:04

about changing the amount

1:10:07

of serotonin and norepinephrine

1:10:10

and titrating those differences. That's

1:10:12

why a lot of people have to try multiple different

1:10:14

combinations of drugs until they find

1:10:16

the one that works for them because their

1:10:19

problem might be more serotonin or

1:10:21

less. Serotonin might be more about norepinephrine

1:10:23

and if it's anxiety related, it probably is

1:10:26

or less. Yeah. I

1:10:28

wonder if that's why SSRIs

1:10:29

didn't do much for me but as a person with

1:10:32

generalized anxiety disorder, thanks very much.

1:10:35

And SNRI was helpful.

1:10:38

What is happening with the norepinephrine

1:10:41

when it comes to anxiety? Is

1:10:43

it going off? Is it? Oh yeah.

1:10:46

I mean like I was saying, norepinephrine is

1:10:48

keeping you awake and it's telling you what to focus

1:10:50

on. So with generalized anxiety disorder, not

1:10:52

only are you awake but you're constantly having to focus

1:10:55

on all the things that are chasing you. Your

1:10:59

attention is on all the things that

1:11:01

could potentially kill you because your brain's trying to

1:11:03

keep you alive but it thinks that everything is

1:11:05

trying to kill you so you have to pay attention to everything

1:11:08

and then there's all the things and it gets really overwhelming because

1:11:11

everything is trying to kill you and it's like living in

1:11:12

Australia but yet it's you know, this

1:11:16

is like a terrible cycle for brains to

1:11:18

get into. Australia. The

1:11:21

land of sharks and snakes and spiders

1:11:24

and angry kangaroos. I

1:11:26

guess an angry kangaroo too

1:11:28

who gives you just one star. Oh look kangaroo

1:11:31

too, I said your name again and you loved it.

1:11:33

I feel like perhaps you're

1:11:35

very empathetic to this particular

1:11:38

problem. It might be that I have experienced

1:11:40

that before. And so

1:11:43

does an SNRI, does it, what

1:11:45

exactly is it doing to norepinephrine if it's a

1:11:48

selective norepinephrine reuptake

1:11:50

inhibitor? Is it good to have

1:11:52

more norepinephrine between the cells? Yes,

1:11:55

it can be but it depends on the comparison

1:11:58

levels to the other neurotransmitters.

1:11:59

Okay. Right. So

1:12:02

you're trying to balance dopamine, serotonin, norepinephrine

1:12:05

and get that right cocktail so

1:12:07

that you get a harmony instead of a discordant

1:12:10

dysfunction, if that makes sense. That does

1:12:12

make sense. I didn't realize that SNRIs

1:12:14

and anxiety, that

1:12:16

could be a good link. I always thought,

1:12:19

if I've got anxiety, why do I want more goddamn

1:12:22

norepinephrine

1:12:22

and my synapses? I didn't. That

1:12:25

was me screaming in my own brain. Yeah.

1:12:29

So yes, SNRIs affect both the

1:12:31

norepinephrine and the serotonin and

1:12:33

it's the balance that can be helpful.

1:12:35

Although the first few weeks on an SNRI

1:12:38

can be rocky as hell and more stressy

1:12:40

as your brain adjusts and then becomes

1:12:43

more chill. So my brain asked

1:12:45

me to tell your brain that as

1:12:47

a heads up. Nicky, first time question asker,

1:12:49

asked, is the dopamine pathway activated when

1:12:52

you eat an

1:12:52

Oreo while studying like

1:12:54

it would be when you smoke a cigarette? What

1:12:58

is that Oreo question? Okay.

1:13:00

So I'm going to assume that the reason we're talking about Oreos

1:13:03

is because there is a paper that showed that mice

1:13:05

prefer Oreos to cocaine. And

1:13:07

then it was used in mainstream media

1:13:10

to promote many popular

1:13:12

but scientifically irrelevant headlines

1:13:15

like sugar is more addictive

1:13:17

than cocaine and a bunch

1:13:20

of

1:13:20

other things. So I'm just going

1:13:22

to substitute Oreo for

1:13:25

Parmesan goldfish, which is what I

1:13:27

eat when I'm studying. And

1:13:31

yeah, very, very different things. So we're

1:13:34

talking about sugar and carbohydrates and

1:13:36

feeding your brain in a certain way. There's

1:13:38

definitely dopamine release when you're

1:13:41

eating food because that's one of the things that are going to keep

1:13:43

you alive and that's what dopamine is there for.

1:13:46

Have we gotten this point enough? I'm not sure.

1:13:49

Let me reiterate it. Nicotine is released

1:13:51

when you encounter things that keep you alive. The

1:13:54

nicotine completely different. So

1:13:56

nicotine is a cognitive enhancer. So it's probably

1:13:58

helping your prefrontal.

1:13:59

cortex function and it's shown

1:14:02

to help decrease anxiety. So

1:14:05

it's probably interacting in your amygdala

1:14:07

to reduce stress and facilitating

1:14:10

better studying.

1:14:12

Okay.

1:14:13

Side note, just Google Oreo

1:14:15

plus cocaine, that study is

1:14:17

everywhere. It was cited by pretty much every news

1:14:20

outlet in the known universe. And a professor

1:14:22

who worked on the study stated in a 2013 press

1:14:25

release that he, quote, hadn't touched

1:14:27

an Oreo since the experiment. But

1:14:29

it's unclear if that's because

1:14:32

of their addictive implications or

1:14:34

just because watching rats pick

1:14:36

apart any food with their tiny

1:14:38

clawed feet for years on end tends to

1:14:40

kind of tarnish its appeal. Now,

1:14:42

speaking of

1:14:43

full little bellies. So this is

1:14:45

a good segue to

1:14:47

the gut biome and Libby

1:14:49

Miller, Brigid, Emma Hoch Schneider, Kaby

1:14:52

Mabey, Isabelle Christine Hottinger,

1:14:55

Kira Gowan, Mackenzie Campbell, generic Nicky,

1:14:57

Michelle Lees, Eileen, Mackenzie Campbell, Stefan

1:15:00

Williams, Jen Anathas, and Michelle Lee all

1:15:03

asked about

1:15:05

how many of our neurotransmitters are made

1:15:07

in our guts. And do we have any leads

1:15:09

yet on good foods for good neurotransmitters?

1:15:12

Christine Hottinger, that is, how do I eat

1:15:15

myself happy? Well,

1:15:18

actually, there's been a lot of recent studies

1:15:20

on the microbiome and the influence of

1:15:22

food on mood. And we've always known,

1:15:25

even before we identified that the microbiome

1:15:27

was a thing, that diet had a huge

1:15:29

impact on mood. And

1:15:32

of course, we have always talked about sort

1:15:34

of blood sugar

1:15:35

activity and how crashing

1:15:38

after a lot of sugar can influence

1:15:40

our mood and make us depressed. But

1:15:43

what I think that we're really asking about here

1:15:46

is the chemicals that are released by the

1:15:48

gut biome. One of those chemicals

1:15:50

has been shown to be serotonin,

1:15:52

which is like one of the really really big findings

1:15:55

in that field and like in the neuroscience field

1:15:57

too because we thought, oh,

1:15:59

neurotransmitters.

1:15:59

are synthesized in the neurons,

1:16:02

but I guess not always. I guess there

1:16:04

can be serotonin and potentially other neurotransmitters

1:16:07

just kind of floating around in your bloodstream.

1:16:09

Fancy meeting you here. Does it influence

1:16:12

mood? Yes, probably. Are

1:16:14

there particular super foods that

1:16:16

you can eat to raise your serotonin? Probably

1:16:20

not. But what we eat definitely

1:16:23

does influence the different types

1:16:25

of microorganisms and

1:16:27

the ratios of those microorganisms

1:16:29

in our gut. So

1:16:33

I can't tell her what to eat to make

1:16:35

herself happy, but if she finds

1:16:37

a particular type of diet that does

1:16:40

make her happy, she's not just – it's

1:16:42

not all placebo. Right. It's

1:16:44

not just in her head. It's in her gut. Yes, exactly.

1:16:48

I think that's so bananas that so much serotonin

1:16:51

is made in our simmering poo

1:16:54

tubes. Who knew? Who knew?

1:16:56

That's crazy. And I think about that too

1:16:58

sometimes when

1:16:59

I'm on a particular

1:17:02

binge of very, very unhealthy food

1:17:04

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

1:17:07

to readjust the ratios

1:17:09

of gut bacteria because I know that I'm

1:17:11

feeding it a certain type of sugar or just a

1:17:14

lot of sugar that there's

1:17:16

going to be overgrowth of one population

1:17:18

in my microbiome. Right.

1:17:21

And I'm apologizing to the potentially

1:17:24

more valuable and rarer bacteriums

1:17:27

in my gut. Like I'm sorry. I know I'm overfeeding

1:17:29

that.

1:17:29

You know. I feel like if you like

1:17:32

SimCity, you'll love the

1:17:34

gut biome. Oh, yes. That's so

1:17:36

true. It's like real world consequences.

1:17:39

For more on this topic, you can see last

1:17:42

November's microbiology episode with

1:17:44

Dr. Elaine Shao, who herself says

1:17:46

she tries to eat a varied diet. So

1:17:49

give your microbes natural foods that

1:17:51

would help them thrive, i.e. not

1:17:53

Oreos or cocaine, which was

1:17:56

in soft drinks until the early

1:17:58

1900s, which is just

1:18:00

bananas. Okay, speaking of guzzling

1:18:03

up, a few people asked about alcohol. Lindsay

1:18:05

DeFalco, Amelia H. Anna Thompson and Emmanuel

1:18:07

Sanchez asked what's going on in the brain with different

1:18:09

drugs and controlled substances like

1:18:12

alcohol. And Amelia H. wants to know why

1:18:14

is alcoholism an inheritable trait? Oh,

1:18:18

alcohol is so interesting because there's

1:18:20

no like alcohol receptor. Oh,

1:18:23

like it doesn't act on a particular

1:18:25

receptor the way that

1:18:28

I was describing acetylcholine and

1:18:30

nicotine. It like sort of cozies

1:18:33

up to the receptor and it's like soft

1:18:36

influence. Like we would call it allosteric

1:18:38

modulation. Okay. So it doesn't like

1:18:40

bind to the receptor and cause the

1:18:43

receptor to do anything, but it affects

1:18:45

the way that the receptor responds to

1:18:47

the molecules that it's really supposed to

1:18:49

be talking to. So it can

1:18:52

make it open like easier.

1:18:53

So it needs like less

1:18:56

drug or less neurotransmitter before it responds.

1:19:00

So it's very like sneaky and insidious

1:19:02

in terms of the activity in the brain. Alcohol

1:19:05

has, as anyone that has been

1:19:07

drunk, like, you know, it affects your motor

1:19:10

control in your muscles as well. So has more

1:19:12

than just brain effects,

1:19:14

but in the brain it acts in

1:19:17

that allosteric sort of soft power

1:19:20

kind of a way. And does it kind of mess

1:19:23

with frontal

1:19:23

cortex activity? Like does it

1:19:25

in terms of like loss of inhibition

1:19:28

and maybe less control over emotion?

1:19:31

Yeah, it

1:19:33

disinhibits the

1:19:35

inhibitory neurons. Okay.

1:19:38

It's like the act of alcohol is

1:19:40

a double negative. Okay. So it works

1:19:42

on your inhibitory neurons.

1:19:44

Oh, okay. That's

1:19:47

why I won't do anything. So they're normally like on

1:19:49

like I'm inhibiting and I'm doing my job

1:19:51

and then alcohol is like

1:19:53

take a break. Oh no. Yeah,

1:19:55

yeah. Crystal says the alcohol

1:19:57

affects dopamine, serotonin.

1:19:59

GABA, which is a neurotransmitter

1:20:02

that helps maintain calm, and glutamate

1:20:04

pathways, which affect memory. But

1:20:07

just as your college roommate may have just

1:20:09

lived for Friday Jager shots and

1:20:11

you have never finished a beer, different

1:20:13

people have different genetics that

1:20:16

influence how receptors respond to alcohol.

1:20:18

But the main point is it doesn't have to just

1:20:20

affect dopamine to become addictive. And

1:20:23

scientists, they're still figuring out how it all works.

1:20:26

Neuroscience,

1:20:26

it's complicated. Who knew? All

1:20:29

of us, literally all of us. Okay, now

1:20:31

on the topic of substances, a

1:20:33

bunch of people did ask about recreational

1:20:36

drugs.

1:20:38

Jes Boiseta Garcia, Rebecca Landry,

1:20:40

Joe Portofino, Jimin Alonzo,

1:20:42

Kevin List, James Bullio, Cassie,

1:20:45

Kerry Bringham, all kind of asked,

1:20:48

hey, what's going on with recreational or

1:20:50

ritualistic drugs? Like Ayahuasca,

1:20:54

Kevin List asked, what are your thoughts on microdosing

1:20:56

for mental health issues like depression? And

1:20:59

Jes wanted to know, flim flam or not?

1:21:01

Is psilocybin an effective treatment

1:21:03

for medication resistant psychiatric

1:21:06

conditions? So what's going on with

1:21:08

magical things? Magical

1:21:10

things are

1:21:11

like, it's if one aspect

1:21:14

of the orchestra went completely,

1:21:16

like we came on steroids. If

1:21:19

you showed up and there was like 37 cellos.

1:21:26

And like four of all

1:21:29

of the other instruments, whatever that

1:21:31

would sound like, that's kind of what recreational

1:21:33

drugs do. They put things completely

1:21:36

out of balance and

1:21:39

we experience a new

1:21:42

reality through that lens. Like

1:21:44

brains are basically making a guess

1:21:47

at our realities anyway. And so we

1:21:49

experienced a brain's best guess

1:21:51

at what is actually happening right

1:21:54

now. Your whole reality is

1:21:56

just a picture

1:21:56

that your brain has painted based

1:21:59

on what it's

1:21:59

sensing. How weird is that? What

1:22:02

is even real? And so when the

1:22:05

predictions of the brain or the way

1:22:07

that the system that is the brain tries to anticipate

1:22:10

or interpret these completely

1:22:13

out of whack situation,

1:22:15

that's when we get the fun that is

1:22:17

recreational drugs. What happens

1:22:20

with psychedelics? Is it a particular neurotransmitter

1:22:22

that is just going off? A lot

1:22:24

of them are

1:22:26

acting on the serotonin system. Okay.

1:22:29

So serotonin is like

1:22:31

when it's sort of a mod, it's a modulation.

1:22:34

It's more global than a lot of

1:22:36

the other neurotransmitters, I would

1:22:38

say. And so when you've got like a bunch of serotonin

1:22:40

like dumped into the system, you have a lot

1:22:43

of different brain regions that are all like trying

1:22:45

to cope with life. Is that why people will take supplements

1:22:48

like five HTP after they will

1:22:51

do like Molly or something

1:22:53

like that? Yeah, you can deplete the amount because

1:22:55

your brain is synthesizing those molecules.

1:22:57

There's a limited number of them. If you think about

1:22:59

a factory production line, it only goes

1:23:01

so fast so you can only produce so

1:23:03

many toys or so many cars, or you can only

1:23:05

produce so many molecules of

1:23:08

your particular neurotransmitter. And so

1:23:10

if you have taken Molly

1:23:13

or one of these recreational drugs that has dumped

1:23:16

a whole bunch of neurotransmitter into your brain

1:23:18

and you've been like backstroking through those happy

1:23:20

molecules for a while. Oh, the water

1:23:22

is great. It's

1:23:25

time for your brain to go back to normal because it's

1:23:27

no longer getting those signals. There's

1:23:29

like it has nothing left to give literally.

1:23:31

And so giving it some precursors

1:23:34

for the molecules that it needs to replenish is

1:23:36

sort of a way of helping it get back

1:23:39

to normal because you're skipping a few steps

1:23:41

in the assembly line. Got

1:23:43

it. So you're not left like high and

1:23:45

dry, like literally high and

1:23:48

actually dry of the good brain

1:23:50

juices. Now this next topic was

1:23:52

on the minds of patrons. John Arokvik,

1:23:55

Graham Tattersall, Maria, generic Nicky,

1:23:57

Sydney Manzill, Dawn Ewald, first.

1:23:59

Time mindfulness question asker,

1:24:02

Jennifer Tran, and first time question asker, Ashley

1:24:04

Beatty, who wondered about the impact of meditation

1:24:06

on anxiety and depression specifically. And

1:24:09

now what about meditation, yoga,

1:24:11

things like that? Do

1:24:14

you ever use any of it? Do

1:24:16

you feel like you should be using it? I think

1:24:18

that it's definitely a good place to start. I'm

1:24:21

one of those people that

1:24:22

is like, why would you pay for gym membership

1:24:24

if you could just go outside and run? And then

1:24:26

I just stay inside and watch Netflix the entire

1:24:28

time. And that's kind of how I feel

1:24:30

about mindfulness.

1:24:33

Like it's something that you can do quite easily. You

1:24:36

know that there's positive effects. Like there's been

1:24:38

scientific papers that have shown that there are positive

1:24:40

effects of meditation practice,

1:24:43

of mindfulness practice that really does

1:24:45

help quiet some of the overactivity

1:24:48

and the amygdala that we see in like Western

1:24:50

society, for instance. So

1:24:52

why not do it? I

1:24:55

don't do it. I

1:24:58

probably should. It would definitely

1:25:00

help me a lot. So do

1:25:02

as I say, not as I do. Okay, doctor. Okay,

1:25:06

what is your least favorite thing about neuroscience,

1:25:09

about brains

1:25:12

or about your life as a doctor

1:25:15

brain, essentially on TV

1:25:17

and all over the world? Neuroscience

1:25:20

is really hard to do without actually

1:25:23

touching the tissue that you're trying to study.

1:25:25

And so we

1:25:28

use a lot of model brains in order

1:25:30

to learn the things that we learn,

1:25:33

which is really challenging because

1:25:35

a lot of the, even the information that

1:25:37

I was sharing with you today, like we know this

1:25:39

to be true for mice and

1:25:41

rats. And we assume that it is

1:25:44

also true for humans

1:25:46

to the best of our possible ability.

1:25:49

But

1:25:50

as far as I know, we aren't able to like

1:25:53

do the same types of experiments on

1:25:55

humans. So a lot of we

1:26:00

know is inferred. Right.

1:26:03

Would you ever donate your brain to science?

1:26:06

What do you think? I

1:26:08

think I would be a terrible

1:26:10

test subject. I'm

1:26:13

always the outlier. I never

1:26:16

feel that I am a good representation

1:26:19

of the mathematical average of

1:26:21

a human anything. I

1:26:23

feel like my brain would give like

1:26:26

wrong data or like not accurate

1:26:30

data. And I think that actually speaks

1:26:32

to there was an earlier question about like,

1:26:34

why don't we know how these things work?

1:26:36

And it's like, well, we can know things pretty

1:26:39

accurately for a particular breed

1:26:42

of mouse or particular breed of rat because they're

1:26:44

all exactly the same. They're all clones of each other.

1:26:46

So it's really easy for us to know what's going on there.

1:26:48

We can't clone humans. We can't

1:26:51

do research on humans. So all

1:26:53

of the genetic background, all of the environmental

1:26:56

differences,

1:26:56

all of those things mean that

1:26:58

we're really just kind of guessing at what's going to work

1:27:01

for the average population. Isn't

1:27:03

it kind of crazy that we just have clones, like animal

1:27:05

clones running around? Is that kind of weird?

1:27:07

Is that ever creepy out? It doesn't really

1:27:10

creep me out, but I guess because I mostly

1:27:12

work with bacteria and with mice

1:27:15

and they're not,

1:27:16

it's easy to not see

1:27:19

them as necessarily having personalities.

1:27:22

I guess, but I never, I never raised

1:27:25

mice. I was a beneficiary of

1:27:27

people that did mouse experiments, but

1:27:29

I never actually had a colony of mice

1:27:31

that I was raising. And I know that neuroscientists

1:27:34

that do work directly with live

1:27:36

behaving animals would absolutely tell

1:27:38

me that I'm crazy, but they have, they

1:27:41

have personalities and differences, even

1:27:43

though genetically they're the same. Wow.

1:27:46

Do you hear that

1:27:47

Barbara Streisand cloned her dog and she thought

1:27:49

she was getting one and they're like, well, you're four. And she's

1:27:51

like, fuck. She's just like, oh no.

1:27:54

She'd like give it away to like her assistant's daughter

1:27:56

or something. She's like, I didn't, I didn't think I'd get

1:27:58

four of them. It's true.

1:27:59

Barbra Streisand missed her dog, Samantha, so

1:28:02

much that she had four more made

1:28:04

from a swab of her cheek. Now the

1:28:06

runt of that litter sadly died, but

1:28:09

she kept two of the other ones and the third

1:28:11

she says, the 13-year-old daughter of my

1:28:13

A&R man bonded with one of the clones, so

1:28:15

I gave them that puppy. So there you go, clones, they're

1:28:18

all over the place. It is just like not

1:28:20

a biggie. Shrug. What's your favorite

1:28:22

thing about your job or neuroscience

1:28:25

or the brain?

1:28:26

I mean,

1:28:27

I think that we are inherently selfish

1:28:30

and that we really like to know things about ourselves.

1:28:34

And neurosciences is kind of like my

1:28:36

way of trying to understand this like

1:28:38

human condition. So,

1:28:40

you know, brains are where they're really

1:28:43

intense and they want everything to have meaning

1:28:46

and they will ascribe meaning to

1:28:48

things that really there is no

1:28:51

purpose to. And so I think that's

1:28:53

probably just like what I'm trying to do with my

1:28:56

meaningless life is to

1:28:57

figure out, you know, why

1:29:00

humans? And why

1:29:02

me? That's the best

1:29:04

title for a biography. Why

1:29:07

humans? Why us? Oh,

1:29:09

as for neuroscience movies, Crystal says

1:29:12

pretty much none of them get

1:29:14

it right. Like none. And they

1:29:16

all try to make things way too spiritual

1:29:19

and that using only 10% of your brain is

1:29:21

a big hairy smelly myth. And

1:29:23

that the Scarlett Johansson vehicle Lucy was

1:29:26

wall to wall flim flam

1:29:27

and a griches. So she thinks writers

1:29:30

and directors should just focus on the real neuroscience

1:29:32

because it's bananas and it's mysterious

1:29:34

enough.

1:29:35

Reality is stranger than fiction.

1:29:38

And so let's figure out what's actually going on

1:29:40

and how can we tell that story in

1:29:43

an epic but accurate way because

1:29:45

it really is enough to blow your mind. Right.

1:29:48

Your actual mind. Thank you

1:29:50

so much, Dr. Delworth. Thank you for having

1:29:53

me. Okay, so now that you are fully enchanted

1:29:55

by the knowledge of Dr. Brain Crystal

1:29:57

Delworth, you could head to Crystal Delworth.

1:29:59

for links to her social

1:30:02

media and her LinkedIn page. There is

1:30:04

a link to that in the show notes of this episode. And special

1:30:06

thank you to Casey Hanmer for making sure that

1:30:08

she got that domain name. That's crystaldillworth.com.

1:30:11

So go there and follow her on Twitter

1:30:14

and on LinkedIn and on Instagram.

1:30:17

You can also check out Mission Unstoppable on

1:30:19

CBS every Saturday. Now links

1:30:21

will be up at allyward.com slash ologies

1:30:24

slash molecular neurobiology,

1:30:26

including to the charity supported and to the sponsors

1:30:29

making that possible.

1:30:29

We are at ologies on Instagram

1:30:32

and Twitter. I'm at Allie Ward with one

1:30:34

L on both. If you have a picture of yourself in

1:30:37

merch on Merch Mondays, we repost it.

1:30:39

So just hashtag it, ologies merch. I'm

1:30:42

also on CBS every Saturday morning

1:30:44

on Innovation Nation with Mooraka. And

1:30:46

I have my own science show on CW

1:30:49

called Did I Mention Invention, which is on Saturday

1:30:51

or Sunday, depending on where you live in the country. And thank

1:30:53

you to Aaron Talbert for adminning the Facebook

1:30:55

Ologies podcast group and for being amazing

1:30:58

people. Also thank you to Bonnie Dutch and Shannon

1:31:00

Feltes of the comedy podcast You Are That for

1:31:02

handling merch at ologiesmerch.com

1:31:05

and also for being wonderful. Transcripts

1:31:07

and bleeped episodes are at allyward.com

1:31:09

slash ologies dash extras. There'll

1:31:12

be a link in the show notes. Thank you to all the Ologies

1:31:14

transcribers and the Ologies transcribers Facebook group

1:31:17

and Emily White for working on those. And assistant

1:31:19

editing was done by Jared Sleeper of MindJam

1:31:21

Media and the mental health podcast

1:31:23

My Good Bad Brain. He talks about ADHD

1:31:25

a lot on that. So check out My Good Bad Brain. And

1:31:28

thanks, as always, to the brain that stitches

1:31:29

all these pieces together each week, Stephen

1:31:32

Ray Morris, who also hosts the percast about

1:31:34

cats and the dino podcast See Jurassic Right.

1:31:36

And just a little fun fact from 2023, if you're like, wait, Dr.

1:31:40

Dilworth, she has the same last name as Noelle

1:31:42

Dilworth, who works on the show. That is

1:31:44

because, yes, after this episode, I

1:31:46

hired Noelle. She works on the show. She's the best. OK.

1:31:49

The theme music was written and performed by Nick Thorburn of

1:31:51

the band Islands. And that cello music you heard

1:31:53

was the cello song by The Piano Guys.

1:31:55

And they're on YouTube. Now, if you stick around until

1:31:57

the end of the episode, you know I tell you a secret.

1:31:59

My secret is that I had a nightmare that

1:32:02

I was getting shot to space. I was like, oh, I'm an

1:32:04

astronaut, I guess. And beforehand they had

1:32:06

to weigh

1:32:07

everything that went into or came

1:32:09

out of my body. Let's just say it was a little too

1:32:11

close for comfort in my dream. And I woke up so

1:32:13

relieved that I didn't have to pee in a bucket in front

1:32:15

of anyone. Also another secret,

1:32:18

I actually do keep candles in

1:32:20

my wallet because honestly it happened so

1:32:22

often. It's someone's birthday and just being

1:32:24

able to shove a candle and like a piece of

1:32:26

toast or a Snickers, it's such a daymaker.

1:32:29

So they don't take up a bunch of room. I just put

1:32:31

like two or three wrapped up in a little

1:32:33

piece of tinfoil and I wedge them in my wallet.

1:32:36

But I'm pretty sure it looks like something illegal,

1:32:38

but I promise keep a few birthday candles

1:32:40

in your bag and you're gonna use them sooner than you

1:32:42

think. They come in handy all the time. Also, does

1:32:45

NASA even make you pee in buckets or did

1:32:47

I just make that up in a dream? Let me know, okay,

1:32:50

bye bye.

1:32:50

Pack a dermatology, audiology, cryptozoology,

1:32:54

lithology, nanotechnology,

1:32:57

meteorology, phytology,

1:33:00

phytology, seriology,

1:33:03

phytology.

1:33:11

Hey, I came here to be drugged, electrocuted,

1:33:14

and probed, not insulted.

1:33:17

When it comes to hummus, delicious

1:33:19

is in the details and Boer's head's

1:33:21

collection of exceptional hummus flavors is

1:33:23

in a class of its own, expertly

1:33:25

crafted to achieve the perfect balance of

1:33:28

creamy texture and refined taste.

1:33:30

From flavorful roasted red pepper to

1:33:33

decadent dark chocolate hummus, made

1:33:35

for you to savor every delicious

1:33:37

scoop. This is hummus so extraordinary

1:33:40

it can only be from Boer's head. Compromise

1:33:43

elsewhere.