ANDREW HUBERMAN: Welcome to
the Huberman Lab podcast, where we discuss science
and science-based tools for everyday life. [MUSIC PLAYING] I'm Andrew Huberman,
and I'm a professor of nNeurobiology
and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Gina Poe. Dr. Gina Poe is a professor in
the Department of Integrative Biology and Physiology at the
University of California Los Angeles. Her laboratory and research
focuses on the relationship between sleep and
learning, in particular how specific patterns
of brain activity that are present during
specific phases of sleep impact our ability
to learn and remember specific types of information. For instance, procedural
information-- that is how to perform specific
cognitive or physical tasks, as well as encoding
of emotional memories and discarding
emotional memories. Indeed, her research focuses
on how specific phases of sleep can act as its own
form of trauma therapy, discarding the emotional
tones of memories. In addition, her
laboratory focuses on how specific phases
of sleep impact things like the release
of growth hormone. Growth hormone, of course,
plays critical roles in metabolism and tissue repair,
including brain tissue repair, and therefore has critical
roles in vitality and longevity. Today you will learn many
things about the relationship between sleep, learning,
emotionality, and growth hormone. One basic but very
important takeaway that you'll learn about
today, which was news to me, is that it's not
just the duration and depth of your
sleep that matter, but actually getting to sleep
at relatively the same time each night ensures that you get
adequate growth hormone release in the first hours of sleep. In fact, if you require, let's
say, eight hours of sleep per night, but you go
to sleep two hours later than your typical bedtime
on any given night, you actually miss the window
for growth hormone release. That's right. Getting growth hormone
release in sleep, which is absolutely critical
to our immediate and long term health, is not a prerequisite
of getting sleep, even if we are
getting enough sleep. As Dr. Poe explains, there
are critical brain circuits and endocrine, that
is hormone, circuits that regulate not just the
duration and depth and quality and timing of sleep,
but when we place our bout of sleep, that is
when we go to sleep each night, plus or minus about
a half hour or so, strongly dictates
whether or not we will experience all the health
promoting, including mind promoting, benefits of sleep. Today's episode covers
that and a lot more in substantial detail. You will learn,
for instance, how to use sleep in order to
optimize learning, as well as forgetting, for those things
that you would like to forget. So during today's
episode, Dr. Gina Poe shares critical information
about not just neuroscience, but physiology and
the hormone systems of the brain and
body that strongly inform mental health, physical
health, and performance. So by the end of
today's episode, you'll be far more informed
about sleep and how it works, the different roles it
performs, and you'll have several new
actionable steps that you can take
in order to improve your mental health, physical
health, and performance. Before we begin, I'd
like to emphasize that this podcast is separate
from my teaching and research roles at Stanford. It is, however, part
of my desire and effort to bring zero cost to
consumer information about science and
science-related tools to the general public. In keeping with
that theme, I'd like to thank the sponsors
of today's podcast. Our first sponsor is LMNT. LMNT is an electrolyte drink
that has everything you need and nothing you don't. That means plenty of salt,
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livemomentous.com/huberman. And I should just
mentioned that the library of those supplements is
constantly expanding. Again, that's
livemomentous.com/huberman. And now for my discussion
with Dr. Gina Poe. Dr. Gina Poe, welcome. GINA POE: Thank you. ANDREW HUBERMAN: I've
really been looking forward to this conversation because
I'm familiar with your work, and I know that many
people are going to be excited to
learn about your work as it relates to
sleep, as it relates to problem solving, creativity,
addiction and craving, relapse, and a number of other
important topics. So to start things
off, I would love for you to educate us
a bit about this thing that we are all familiar
with and yet very few of us understand, which is sleep. And if you would, could you
describe the various phases of sleep that exist? What distinguish them? And perhaps frame this
within the context of what would a perfect
night's sleep look like? GINA POE: OK. ANDREW HUBERMAN: How long
would it last, more or less, and what would the
biology look like? What is a perfect night's sleep? GINA POE: Yeah, that's
a great question. All right. So sleep is really
different from wakefulness, and in fact can't be replaced
by any state of wakefulness that we've been able
to come up with so far. Our brain chemistry is
completely different. And in the different
stages of sleep, which there is non-REM and
REM are the two major states of sleep, and every animal
we've studied so far seems to have both
of those states. Anyway, those two states are
entirely different from one another, too. And even within non-REM,
there are three states. Stage one, which is what
you slip into when you first falling asleep-- it's dozing. There's kind of an
interesting rhythm that goes on in the brain. It's kind of a
fast, gamma rhythm. And then there's
stage two, which is a really cool state we
sort of used to ignore, sleep researchers, because
it was a transient state between wakefulness
and the deep stage three, slow wave sleep, which
is the most impressively different. And between that and REM sleep. So stage two, I'll talk
a little bit more about. And then the deep,
slow wave sleep state, which is when big, slow waves
sweep through our brain. And now we realize that
it cleans our brain. One of the things that
those big, slow waves do is cleans our brain and does
other really important things to restore us from a
day of wakefulness. And then REM sleep,
which is the most popular because that's where we
have the most active dreams. And when you wake up
someone out of REM sleep, they'll almost always
report having dreamed something really bizarre. That's called REM sleep,
rapid eye movement sleep. So those are the four states
of sleep, of human sleep, and we cycle through them
every 90 minutes or so. When we go to sleep,
say 10:30, 11:00, our first REM sleep period
comes about 105 minutes after we fall asleep and
lasts about 20 minutes. Actually, it comes
about 95 minutes and lasts 10 or 15 minutes. And then we start over again. And we have about five of those
per night for a perfect night's sleep-- four or five,
something like that. So a perfect night's sleep is
seven and a half, eight hours. There was a really
great study that put people in a semi-darkened
room with nothing but the bed for 12 hours
every day for a month. And what people did
initially, because we're in a sleep deprived
nation, is that they slept a lot more than usual,
like 10 or 11 hours of the 12. And then they leveled
off after a week or two to about eight hours
and 15 minutes of sleep. So you actually can't oversleep. I mean, they had nothing
else to do but sleep, and they would round off to
an average eight hours and 15 minutes a night and then spend
the rest of the time twiddling their thumbs, humming tunes-- ANDREW HUBERMAN: Interesting. GINA POE: --daydreaming. ANDREW HUBERMAN:
I want to get back to the contour of a
perfect night's sleep, but I'm intrigued by this idea
that people can't oversleep. I'm often asked whether or
not we can get too much sleep and whether or not sleeping
too long can make us groggy the next day. Is there anything to that? And how does one
determine how long they should sleep on average? GINA POE: On average, yeah. Well, that's interesting
because different people seem to need different
amounts of sleep, but we don't really even know
exactly what sleep is for. So what they need is kind of-- it's murky. So we do know a lot of things
that sleep does now for us, but we don't know how
long those things take. So how long we need to sleep is
also just a big question mark. But some people
don't feel rested until they've slept nine hours. Some people don't feel rested
after three or four and a half. But most people, if they
consistently deprive themselves of sleep so that
they're only sleeping for four and a
half hours a night, build up a cognitive deficit
that just builds up over time. The more nights you have with
sleep deprivation, the more cognitive deficit you have. And so you need sleep, again,
to sleep more to recover. Now, the question
you had about um-- ANDREW HUBERMAN:
Can you oversleep-- GINA POE: Can you
oversleep, right. ANDREW HUBERMAN: Can
you sleep to the point where it's too much? You know, growing up,
when I was in high school, my girlfriend's
dad had this belief that no one should
sleep in past 6:00 AM. So he would wake all the-- there were two
children in the home. He would wake up the
kids in that house. He had this thing
against oversleeping, regardless of when
people went to sleep, and I always thought that
was an interesting mentality. GINA POE: Yeah. It's not terrible, actually,
because what that will do is it will make you
sleepier the next night to get to bed on time. So it'll build up
your homeostatic need if you wake up too early. But so I don't think
you can oversleep. But people who sleep
a lot, like people who sleep over nine
hours, it's probably indicative of some other
problem because in fact, if you have a lot of
different conditions, it will cause you
to sleep a lot more. Probably because
what it does is it interferes with your
efficient sleep, the efficiency of your sleep. So if you find yourself
sleeping consistently nine hours plus every night,
then you might want to consult a doctor about
maybe what else it might be. It could be cancer. It could be sleep apnea,
which affects a lot of people. It could be that your
sleep is super inefficient because you're snoring a
lot more than you know, or you're waking up a lot more
than you know every night. So you might want
a sleep study just to see how your
sleep is, and then see what else might be
causing you to sleep so much. ANDREW HUBERMAN:
And that wouldn't be if somebody is
sleeping nine or 10 hours every once in a while. You mean if they're
consistently sleeping for more than nine hours. GINA POE: If they feel
like they need it in order to function cognitively
the next day, it might be that your sleep
is just not efficient, and you might want to look
into why that's the case. ANDREW HUBERMAN: Interesting. Forgive me for the anecdote,
but I can't resist. Years ago I went to
an acupuncturist, and he gave me these
red pills, of which I don't know what they contained. GINA POE: Uh-oh. ANDREW HUBERMAN: But I took
them because he told me they would help with my sleep. GINA POE: OK. ANDREW HUBERMAN: And
I would fall asleep about 30 minutes
after taking them, and I would have
incredibly vivid dreams. And I'd wake up
four or five hours after having gone to sleep
feeling completely rested, something that I've
never really experienced on a consistent basis. I want to do mass
spec on these pills. I still have no idea what
was in them, whatsoever. GINA POE: I want to do mass
spec on those pills, too. ANDREW HUBERMAN: Yeah, exactly. Some people thought perhaps they
had GHB, gamma hydroxybutyrate, which is, by the
way, an illegal drug. It can kill you. It's not something
you want to take. GINA POE: No, that's not good. ANDREW HUBERMAN: But anyway,
if ever someone can figure out what the red pills
were, I'll be very-- GINA POE: That's really great. ANDREW HUBERMAN: And this is
not a red pill of the other sort red pill. This is just the
red sleep pills. GINA POE: Interesting. I mean, it could have
been even a placebo effect because placebo is
extremely strong. ANDREW HUBERMAN:
Although, I don't know. There was really something
to these red pills. So shout out to
the acupuncturists in Eastern medicine. But to return this to this
idea of the architecture of a perfect night's sleep. So you said we fall asleep. The first 90 minutes of sleep. REM sleep, rapid
eye movement sleep, will arrive at
about 95 minutes in. Does that mean that the
rest of that 90 minutes is consumed with
slow wave sleep? GINA POE: Yeah, non-REM sleep. ANDREW HUBERMAN: OK. And what about the sleep
where we are lightly asleep, and we might have a
dream that has us somehow thinking about movement or
that we jolt ourselves awake? That often happens early
in the night, right? GINA POE: Yeah, that's
the first stage-- stage one and
stage two of sleep. And stage two sleep
is really cool because that has something
called sleep spindles and K-complexes. And what sleep spindles are are
a little bit of activity that's 10 to 15 hertz in frequency. It's a conversation between
the thalamus and the cortex. The thalamus is the
gateway to consciousness, and the neocortex processes
all our cognition. And so it's these spindles. They're called sleep spindles. And if you wake up
out of that state, you will often report a dream,
like a hallucination style dream. It won't be a long dream report
like you have out of REM sleep, but it will be some
hallucination state. And while we're
falling asleep, one of the reasons we
call it falling asleep is because in stage
one and stage two our muscles are relaxing. And if there's part of our
brain that's conscious enough to sort of recognize
that relaxation, we'll feel like we're
falling, and we'll jerk awake. So often that hallucination--
it's called hypnagogic hallucination-- will feel like-- it'll include some
falling aspect that we'll wake up out of. ANDREW HUBERMAN: That's
really interesting to me. I've long felt that
sensation of almost, like, dropping back into my head. So much so that if I elevate
my feet just slightly and I tilt my head back
just slightly in order to go to sleep, I find that
I fall asleep much faster. GINA POE: Interesting. ANDREW HUBERMAN:
But it does feel as if I'm going to
fall, like, almost going to do a backward somersault.
I actually really like the sensation and
usually because it precedes falling deeply asleep. GINA POE: Yeah, that's
really interesting. Somebody has to do a study
of elevated feet and-- ANDREW HUBERMAN: Yeah, there's
a little bit on body position and sleep in some of the
washout that we'll talk about. So early in the night you've got
these lighter stages of sleep, less rapid eye movement sleep. What can we say about the
dreams that occur during the, say, first and second
90-minute cycles of sleep. Are they quite different
than the patterns of sleep and dreaming that
occur later in the night or toward morning? GINA POE: Well, OK, that's
an interesting question, and there's a lot
of facets to it. There is some evidence that
the first four hours of sleep are very important
for memory processing. And in fact, if you've
learned something new that day or have experienced a new
sensory motor experience, then your early
sleep dreams will incorporate that experience
much more than the later sleep dreams. Later, as that memory
gets consolidated from the early
structures, which are the hippocampus deep in the
temporal lobe to the cortex in a distributed
fashion, that memory seems to move from that
hippocampus to the cortex. And also the dreams that
incorporate that memory also move later in the night. So nobody knows
why, but it does. There was a great study
by Siddhartha Ribeiro who studied the consolidation
of memories from the hippocampus to the cortex in a rat across
the period of a full day's sleep because rats
sleep in the daytime. And he found that each
subsequent REM sleep period moved that memory
from the hippocampus to the first area
that projects to it, and then the second area,
and then the third area. And you can see the memory
moving throughout the sleep period. ANDREW HUBERMAN: Cool. Very cool. I have to read that study. So there's a number of
different hormones associated with the different
stages of sleep. We know that melatonin
is a hormone-- GINA POE: Of nighttime. ANDREW HUBERMAN: --of
nighttime that makes us sleepy. What about growth
hormone release? When does that
occur during sleep? GINA POE: So growth
hormone release happens all day long
and all night long, but the deep, slow
wave sleep that you get the very first
sleep cycle is when you get a big bolus
of growth hormone release, in men and women equally. And if you miss that first
deep, slow wave sleep period, you also miss that big bolus
of growth hormone release. And you might get, ultimately
across the day, just as much overall growth hormone
release, but endocrinologists will tell you that big
boluses do different things than a little bit
eked out over time. So that is what we know. There's also a big push
to synthesize proteins. So that's when the
protein synthesis part that builds memories,
for example, in our brain happens in that
first cycle of sleep. So you don't want to miss
that, especially if you've learned something really big
and needs more synaptic space to encode it. ANDREW HUBERMAN:
How would somebody miss that first 90 minutes? GINA POE: Sleep
depriving themselves. Yeah. ANDREW HUBERMAN: So
let's say I normally go to sleep at 10:00 PM. And then from 10:00
to 11:30 would be this first phase
of sleep, and that's when the big bolus of growth
hormone would be released. Does that mean that
if I go to sleep instead at 11:30 or
midnight that I missed that first phase of sleep? Why is it not the case that I
get that first phase of sleep just simply starting later? GINA POE: It is
a beautiful clock that we have in
our body that knows when things should happen. And it's-- every cell
in our body has a clock. And all of those clocks
are normally synchronized. And those circadian
clocks are synchronized. And so our cells are ready to
respond to that growth hormone release at a particular time. And if we miss it-- and it's a
time in relation to melatonin also-- so if you miss it, yeah, you
might get some growth hormone release. But it's occurring at a time
when your clock has already moved to the next phase. And so it's just a clock thing. ANDREW HUBERMAN: Yeah. I don't think we can overstate
the importance of what you just described. And to be honest,
despite knowing a bit about the sleep research
in circadian biology, this is the very first time
that I've ever heard this that if you normally go to sleep
at a particular time and growth hormone is released in
that first phase of sleep, that you can't simply
initiate your sleep out later and expect to capture
that first phase of sleep. GINA POE: Yeah. ANDREW HUBERMAN:
That's incredible and I think
important and as many listeners are probably realizing
also highly actionable. So what this means
is that we should have fairly consistent
bedtimes in addition to fairly consistent wake times. Is that right? GINA POE: Exactly. And in fact, one
of the best markers of good neurological
health when we get older is consistent bedtimes. ANDREW HUBERMAN: Wow. OK. I don't want to backtrack. But I did write down
something that I think is important for me to
resolve or for you to resolve. So I'm going to ask
this people that sleep nine hours or more perhaps
that reflecting an issue-- some underlying
issue, perhaps, is being a teenager
or an adolescent and undergoing a
stage of development where there's a lot of
bodily and brain growth and exception to that, because-- GINA POE: Yes. ANDREW HUBERMAN: --I don't
recall sleeping a ton when I was a teenager. I had a ton of energy. But I know a few teenagers. And they sleep a lot. GINA POE: Yeah ANDREW HUBERMAN: Like they'll
just sleep, and sleep, and sleep, and sleep. Should we let them sleep,
and sleep, and sleep? GINA POE: Let them sleep. ANDREW HUBERMAN: OK. So that's the one exception. What about-- GINA POE: Just like babies. ANDREW HUBERMAN: OK. GINA POE: When you're developing
something in your brain or the rest of your
body, you really need sleep to help
organize that. Sleep is doing really hard
work in organizing our brains and making it develop right. And if we deprive
ourselves of sleep, we will-- actually,
also just like I said, we have a daily clock. We also have a
developmental clock. And we can miss a
developmental window if we don't let ourselves
sleep extra like we need to. ANDREW HUBERMAN: What other
things inhibit growth hormone release or other components
of this first stage of sleep? In other words, if I
go to sleep religiously every night at
10:00 PM, are there things that I, perhaps,
do in the preceding hours of the preceding day
like ingest caffeine or alcohol that can make that
first stage of sleep less effective even if I'm
going to sleep at the same time? GINA POE: Alcohol definitely
will do that because alcohol is a REM sleep suppressant. And it even suppresses
some of that stage two transition to REM with
those sleep spindles. And those sleep
spindles, we didn't talk about their
function yet, but they're really important for moving
memories to our cortex. It's a unique time
when our hippocampus, like the RAM of our brains,
writes it to a hard disk which is the cortex. And it's a unique time
when they're connected. So if you don't
want to miss that, you don't want to miss
REM sleep when it's also a part of the consolidation
process and schema changing process, and alcohol in
there before we go to sleep will do that. Until we've metabolized alcohol
and put it out of our bodies, it will affect our sleep badly. ANDREW HUBERMAN: So
probably fair to say no ingestion of alcohol
within the four to six hours preceding sleep? GINA POE: Yeah. ANDREW HUBERMAN:
Given the half life? GINA POE: Given the half-- ANDREW HUBERMAN: Or at all--
or at all would be better. But I know some people
refuse to go that way. GINA POE: And maybe
a little bit is OK. I don't know what
the dose response is. But there are studies out
there you can look at. ANDREW HUBERMAN: Great. GINA POE: Yeah. ANDREW HUBERMAN: So we're still
in the first stage of sleep. And I apologize for
slowing us down. But it sounds like it's
an incredibly important, first phase of sleep. What about the second and third
90-minute blocks of sleep? Is there anything that
makes those unique? What is their signature
besides the fact that they come second and third in the night? GINA POE: There's more
and more REM sleep the later the night we get. There's also a
change in hormones. The growth hormone and melatonin
levels are starting to decline. But other hormones
are picking up. So it is a really
different stage that you also don't want
to shortchange yourself on. And I think that's the stage
many studies are showing that those are the
times in sleep when the most creativity can happen. That's when our dreams can
incorporate and put together old and new things
together into a new way. And our schema are
built during that time. So yeah, we can
change our minds best during those phases of sleep. ANDREW HUBERMAN: Could you
elaborate a little bit more on schema? GINA POE: Yeah. ANDREW HUBERMAN: No one-- I don't think anyone
on this podcast has ever discussed schema. I'm a little bit
familiar with schema from my courses on psychology. But it's been a while. So maybe you could just
refresh mind and everyone-- GINA POE: Well, it's
still a concept. ANDREW HUBERMAN: Sure. GINA POE: Schema-- ANDREW HUBERMAN: How do you--
how do you define schema? GINA POE: Right. I think of schema as-- like we have a schema
of Christmas, right? We have all kinds of ideas
that were so together and called Christmas,
a holiday season. In the northern
hemisphere, it's cold. We have Santa Claus, and
reindeer, and jingle bells, and even things that are
false but we normally associate with Christmas
presents, family gathering when it is. All of this stuff is
sewn together into one-- there's a thread
linking them all. And we can just give ourselves a
list of words, and none of them contain the word Christmas. And then ask people later,
give them another list of words and include the word Christmas. And they'll say, oh,
yeah, that word was there, because in their
minds they brought up that word, Christmas, because
it's part of that whole schema. So that's what-- it's
sort of a related-- lot of related
concepts, I guess. ANDREW HUBERMAN: I think about
the desktop of my computer would scare some people. But it's just a ton of folders. GINA POE: Yeah. ANDREW HUBERMAN: But
each of the folder names mean something very
clear and specific to me. GINA POE: Right. ANDREW HUBERMAN:
And inside of those folders are collections
of things that make sense in terms of how they're batch. Is that one way to think about-- GINA POE: No, that's a
great way to think of it. And when you're in REM
sleep in the later parts of the night and that
transition to REM, that's when your
computer of your brain is opening folders and comparing
documents, seeing if-- is there anything the same? These two documents
look very much the same, but there's a little
bit of difference. And it can link
those conceptually. So that's probably one of
the origins of creativity is finding things
that are related, maybe just linked a little bit. And you can find that
link and strengthen it if it makes your schema
interesting and different. ANDREW HUBERMAN: Yeah,
very interesting. Many people, including
myself tend to wake up maybe once during
the middle of the night to use the restroom. I've tried to drink less
fluid before going to sleep. I've heard also that the impulse
to urinate, forgive the topic, but a lot of people deal with
this, so the impulse to urinate is also dictated by how quickly
you drink fluid, not just the total volume. So I've switched
to sipping fluids more slowly from my last
beverage of the day which seems to help. But the point here is that
I think a lot of people wake up once in the middle
of the night oftentimes to use the restroom but
oftentimes just around 3:00 AM and might be up
for a few minutes, hopefully not on their phone or
viewing any bright light which can cause more wakefulness,
but then go back to sleep. Is there any known detriment to
this middle of the night waking or should we
consider it a normal feature for some people's
sleep architecture? GINA POE: Yeah. I think we shouldn't
worry about it actually. I think sleep is really
incredibly well homeostatically regulated. And so really, don't worry
about how much you're sleeping, as long as you're
not intentionally depriving yourself of sleep
by doing something really rewarding and exciting
because even that is stressful to your body and
deprives you of a lot of things we're talking about. So don't worry about it. It's absolutely normal
to wake up at least once in the middle of the
night to go to the bathroom. And as long as you
can get back to sleep in a reasonable
amount of time or even if it takes you an hour,
don't worry about it, as long as you have a lifestyle
that allows you to then make up that sleep either the next
morning or the next night or going to bed
a little earlier. ANDREW HUBERMAN: So if
I understand correctly, there's a little bit of
asymmetry to sleep that catching that first phase of
sleep it's like you either get it or you don't. And you have to get
it by going to sleep essentially the same time each
night, maybe plus or minus 15 minutes or so. GINA POE: Yeah. ANDREW HUBERMAN: But then
if I wake up in the middle of the night and go back
to sleep I cannot catch up, but I can gather all the sleep
that I would have gotten had I just slept the whole
way through the night. Is that right? GINA POE: Yeah, yeah, yeah. And we don't know
actually the answer to whether or not the sleep in the
middle between that early sleep and the late sleep is, in fact,
different for another reason. And whether depriving
yourself of sleep from say, 1:00 to 2:30 in the morning
is bad in a different way, we don't know. ANDREW HUBERMAN:
Well, I suppose I am the experiment in
that case, because I do tend to wake up once per night. And I've come to recognize
it as part of my normal sleep architecture. I don't obsess over it. I do notice that when
I go back to sleep and especially toward morning
that my sleep is incredibly deep. My dreams are incredibly vivid. GINA POE: That's great. ANDREW HUBERMAN: I don't
always remember them. But what is unique, perhaps,
about the architecture of dreams and
sleep in the, let's say the last third of the
night or the second half of the night? GINA POE: Right, yeah. In the second half
of the night, we have longer REM sleep periods. And those are considered
the deepest sleep, even though slow wave sleep, big
slow wave is considered deep. It is deep. ANDREW HUBERMAN: They call
slow wave sleep deep sleep and REM sleep rapid. But now, you're telling me
that REM sleep is actually the deeper sleep? OK. There needs to be
a new nomenclature of sleep researchers. GINA POE: You really shouldn't
call it deeper night. ANDREW HUBERMAN: No, please. GINA POE: The
reason why they call slow wave sleep deep
sleep is because it's difficult to arouse
people out of that state. And when you do arouse
them out of that state, they are most often confused and
just want to go back into sleep and can go back pretty easily. If you arouse someone
out of REM sleep, they're more likely to
report something that was really almost like wakefulness. It was so vivid. But in fact, if you give
someone a non-threatening kind of stimulation like somebody
dropping keys, or a ping, or something like that,
instead of waking-- that same volume will wake
someone up out of non-REM sleep but out of REM sleep and instead
lengthen the amount of time or make it even more dense-- your rapid eye
movements more dense. And often people will
incorporate that sound into their dreams. ANDREW HUBERMAN: So the
body and brain are somehow conscious of the of the sound. And I've heard also
smells can even make it into our dreams in REM sleep. But that it doesn't rouse us-- GINA POE: It doesn't
arouse us as often, yeah. ANDREW HUBERMAN: Interesting. GINA POE: And maybe one of
the reasons why REM sleep is deeper especially in adults
and older people, that deep slow wave sleep goes away. So it's not as deep. It's not as big. The slow waves aren't as large
which is probably problematic, but we are not sure. And so then REM sleep
becomes the deepest stage. Actually in children,
it's kind of a toss up, because it's really
hard to wake them up out of that deep slow wave sleep. And in fact, fire alarms
don't wake them up, even really loud fire alarms
out of that state of sleep. So that's why they're trying
to change fire alarms so that instead of something
that the kids don't associate with anything like the,
whatever, they don't associate them, it says their
name or something else that may be less loud
but more salient to them and will wake them up. ANDREW HUBERMAN: I don't
know having carried sleeping children
in from the car, I don't know that I want
children to start waking up from sleep because that's
one of the best things when we get home and the kids
are asleep in the backseat. You can literally throw
them over your shoulder, gently of course, and
put them to sleep. They are completely out. GINA POE: Yeah, it's wonderful. ANDREW HUBERMAN:
It is wonderful, one of nature's gifts. I'd like to take a quick
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packs and the year supply of vitamin D-3 K-2. So this enhanced
volume or proportion of rapid eye movement sleep in
the second half of the night relates to more
elaborate dreams. We are paralyzed during
REM sleep, correct? GINA POE: Yes,
normally paralyzed. And that's really
good, because that's the time when we're actively
dreaming storyline dreams. And we could hurt ourselves. We're actually really cut
off from the outside world in terms of responding
to, say, this table, or window, or a door. And so different from
sleepwalking which is out of slow wave sleep. And out of slow wave
sleep, that sleepwalking is a mixture between
sleep and wakefulness. So you actually will
respond to the door, or you can cook a full meal,
drive your car while you're in deep slow wave sleep. It's scary, because you never
know what you're going to do. You don't have voluntary,
involuntary control over it. You have no conscious
control over it. But you can actually
safely navigate some situations in
sleepwalking and actually have a conversation. Although, it may not make
much sense when you're sleep talking. In REM sleep, you're not
processing the outside world. And instead, when you're
acting out your dreams, you could be doing things like
walking through a plate glass window or falling off of down
the stairs, things like that. So you really want
your muscles to be inactivated during REM sleep. Otherwise, you will
act out those dreams and really hurt yourself
or your bed partner. ANDREW HUBERMAN: What about
sleep talking or talking in sleep? I don't know how many
relationships have been saved by sleep talking. But I'm guessing a few
have been destroyed. And I'm guessing that talking
in sleep could have meaning or perhaps has no
meaning just as dreams could have meaning or no
meaning, as we recall them. GINA POE: Yeah. Do not take sleep talking
seriously no matter what people say. It doesn't necessarily
reflect truth. So it's not like you're
being more truthful when you're sleep talking. ANDREW HUBERMAN: You just saved
a number of relationships. GINA POE: I hope so. ANDREW HUBERMAN: I'm not
directing this at anyone in particular. But I guarantee you just did. Noted. So as people start to
approach morning or the time when they normally
would wake up, I've heard that it's
important to, if possible, complete one of these 90-minute
cycles prior to waking up. That is if you set
your alarm for halfway through one of these 90-minute
cycles that come late in the night of sleep,
that it can lead to rather groggy patterns of waking. So I'll just ask you directly. Do you use an alarm clock? GINA POE: I do not. Thankfully, I'm
in a line of work that doesn't require me
normally to do anything at any particular time. I do it when I do it. Unless I have to
catch a plane and then I always set my
alarm just in case. ANDREW HUBERMAN: Well,
as a fellow academic, I can tell you there are
plenty of punishing features about being an
academic scientist that offset the fact that you don't
have to use an alarm clock. But it is nice that you can
often set your own schedule. So would you recommend
that if possible that people not
use an alarm clock? GINA POE: Yeah, absolutely. If you can just
listen to your body and wake up when you need to
wake up, that would be great. But one of the reasons why we
have such a grogginess, it's called sleep inertia
when we wake up out of the wrong state which
is deep slow wave sleep, is because-- I liken it to like a
washing machine cycle. This 90-minute cycle is like
a washing machine cycle. And the first part is
to add water, right? And then your clothes
are soaking wet. You don't want to open
the washing machine and try and function, put
them on, and wear them around while they're soaking
wet and full of soap. So you have to wait until
the cycle is through before you can, well, actually,
let's put it in the dryer, too, before you
want to wear them. So yeah, you can function. It just takes a little
while for those clothes, that brain to dry out, so you
can actually function well. But it's better to wait through
the whole cycle is complete. And so that's why
you want to set that 90-minute, alarm clock. And again, that's
around 90 minutes because the first stage of
sleep, the first cycle of sleep is actually a little longer,
more like 105, 110, minutes. But then the second
ones and third ones, they get shorter and shorter
as the night goes on. And in the last
few cycles, you're just doing the end to REM sleep
cycle which takes less time. And if you wake up
out of REM sleep, there's usually no
problem cognitively. You're good to go. ANDREW HUBERMAN: Are you
a fan of sleep trackers? GINA POE: Sure, yeah. ANDREW HUBERMAN: Do you use one? GINA POE: I have one on. I don't take-- I don't live my life
by them, because they are-- the best ones
right now are about 70% effective at staging your sleep. So 70%, it's OK, it's OK. But take it with a grain
of salt is what I'm saying. ANDREW HUBERMAN: Yeah. I've tried various ones. And I compare the
mattress based one to-- actually wear it on my
ankle instead of my wrist. And I do find it informative. But a colleague of
mine at Stanford, Ali Crum, who works on mindset
and belief effects talked to me about a study they
did where people often will bias their sense
of daytime wakefulness based on their sleep score more
than their subjective score. In other words,
if they were told they got a poor night's
sleep, even if they got a great night's sleep-- and this was of course
measured in the sleep lab so they were able
to compare-- people report feeling more groggy. And the opposite is also true
that if it says 100% or 90% on your sleep score,
then people go, oh, I feel great, even though they
might not have slept well. So this speaks to the, I don't
want to say placebo effect, but the belief effects that
are woven in with a score. GINA POE: Yeah. That's right. ANDREW HUBERMAN:
So it seems to me that combining subjective
and objective data is probably best. GINA POE: And I do believe
that you should trust your own physiology and the way that
your body is telling you to feel because in fact, it used to
be that people with insomnia weren't-- were often not believed because
you put them in a sleep lab, and they look like
they slept great. And you wake them
up in the morning, they say, oh, I didn't
sleep very well at all. And that's because
probably we just came out with a paper that shows that
subcortical structures can be in a completely
different sleep state than cortical structures which
is what we measure in the sleep lab what the cortex is doing. ANDREW HUBERMAN: Interesting. GINA POE: So it
might be that people who say, I did not sleep
all night long even though the cortex is saying,
oh, no, you had great sleep, was because they're
monitoring their subcortical, hypothalamus, hippocampus,
thalamus, other structures that the sleep lab
just can't access unless you have depth electrodes
which nobody really wants. ANDREW HUBERMAN: Right. Because that requires holes
in the skull and wires. Wow. So does that mean that the last
50 plus years of sleep science is potentially
flawed in some way, because they're only
recording from-- I guess this would
be the analogy would be-- it's like
recording from the surface of the ocean as opposed
to the depth of the ocean. GINA POE: Right. And trying to ascertain the life
moving down deep in the depth-- ANDREW HUBERMAN: Brace
yourselves colleagues at Stanford sleep
lab and elsewhere. But please just tell us
because I think scientists want to know the truth. GINA POE: Yeah. It's not for nothing
that you want to know what the
cortex is doing. The cortex is really
important for a lot of things. But it doesn't
necessarily tell you what a lot of other really
important parts of the brain are doing in terms of sleep. But there's hope, because
in fact, it would be great. I think that's possible, from
the paper if you look at it, it's in PNAS this year, that
you could detect subtle changes in the cortical
EEG that might be able to tell you what the
subcortical structures are doing. Things like the absolute
power in that sleep spindle band, that
sigma band would change if the hippocampus is in
REM sleep and the cortex is in that sleep spindle
state and vise versa. So there is some
hope that we can gain from people with
depth electrodes or animals with depth electrodes that we
could backwards machine learn what the cortex might
be able to tell us about subcortical structures
from the cortical EEG, so. ANDREW HUBERMAN: Interesting. This is going to be a
stimu-- yes, stay tuned. It's going to be a stimulus for
development of new technology which is always going to
assist in scientific discovery. There is one more
thing I wanted to ask about the architecture
of the night sleep in terms of early
part of the night. Earlier, you
mentioned the washout of debris and the
so-called lymphatic system, I think is what
you're referring to. Could you tell us
a little bit more about the washout that occurs
in the brain during sleep, what that is, and what
roles it's thought to serve, and perhaps if there are any
ways to ensure that it happens or to ensure that
it doesn't happen, and obviously we
want this to happen? GINA POE: Yeah. All right, great question. We talked about
the circadian clock and how certain things
happen at certain times. Well, one of the
things that happens when we're awake and
talking to each other is that there's a
lot of plasticity. There's something that I'm
learning from you today. And you're learning from me. And that changes
our synapses, and it changes the way our proteins are
going to be folded and changed during sleep. It unfolds. This process actually uses a
lot of ATP, the power structure the fuel of the brain. And it unfolds also proteins
while we're doing this, while we're using them. And so during that first part
of the night, when we first fall asleep in the
first 20 minutes or so, we're building that
adenosine back into ATP. And that's probably
why power naps are called power naps,
because we're actually rebuilding the power. And then we're also cleaning
out through the deep slow waves of slow wave sleep. We're cleaning out all
those misfolded proteins, unfolded proteins,
and other things that get broken down and
need to be rebuilt when we're asleep because of
its use during wakefulness. So I liken that to having a
big party during wakefulness. And you need all those
partygoers to leave in order to do the cleanup. And so what I think the
mechanism is, and this is still something to be
tested, is actually slow waves themselves
which is bad news for us as we get older. And those slow
waves get smaller. And so your sleep goes away. So what happens when a neuron
is firing is that it expands, the membrane expands a little
bit, becomes more translucent. That's how we know--
one of the ways we know that neurons
expand when they fire. And so every action
potential, the membrane expands a little bit, as sodium
brings water into the cell. And then when they're
silent, they contract. And so during slow
waves, the cool thing is that the reason why
you can measure them is that all the neurons
at the same time-- not all of them but a
good portion of them-- are firing at the same time
and silent at the same time. And so you think about that
as contracting and expanding all at the same time. It's like a bilge
pump of the brain. So that can pump out-- glia are also really
important for this in terms of cleaning up
debris and transferring it to where it needs to go. So I think of it
actually as a bilge pump cleaning out our brain. ANDREW HUBERMAN: Interesting. I've heard about the lymphatic
system and lymphatic wash out. I've never thought about
the mechanical aspects of it before. I always thought that for
some reason that now it's obvious to me, there had to be
something mechanical but only now that you've
educated me about this. I thought that for some reason
the cerebral spinal fluid just starts washing through. But here, you're talking
about literally an expansion and a contraction of
the neurons in unison and pushing the fluid
through, cleaning out any misfolded proteins
or debris that might occur on the basis of
these metabolic pathways. And the consequence
of that is to, what, to leave the brain in a
state of more pristine action for the next day. is? That right? GINA POE: Yeah you think
of it, again, like a party. And if you don't clean
up after that party and you try and hold
another one the next day, it's going to get more clogged. People have a harder time moving
around and enjoying themselves. And if that builds
up day after day, it's going to be cognition. That would be the
partygoers moving around becomes hard, yeah. ANDREW HUBERMAN:
And so this bilge pump that you
describe is associated with the big slow
waves of deep-- well, of slow wave sleep. So this is going to occur more
or less in the first third of the night, is that right? GINA POE: That's right. ANDREW HUBERMAN:
And are there things that inhibit this process
and are there things that facilitate this process? GINA POE: Yeah. So well, one thing to inhibit
is not to get it but-- ANDREW HUBERMAN: Right. And here, too-- sorry
to interrupt but-- and is this similar to the
case with growth hormone where if you go to sleep
later than you would normally, you miss the washout? GINA POE: Yeah. ANDREW HUBERMAN: It's
not you don't delay it. You miss-- you
missed the washout. GINA POE: That's right. That's right. So if you go to sleep at
1:00 or 2:00 in the morning, your sleep is still going
to be dominated by N2, NREM sleep not by
slow wave sleep. So you need to-- you need to get that
first bit of sleep. ANDREW HUBERMAN:
Would a caveat to that be if somebody normally goes
to sleep at 1:00 or 2:00 AM and wakes up at 10:00 AM
if that's their normal sleep cycle-- GINA POE: Yeah. That should be OK. It should be OK. You would probably want to do-- somebody would want to do
a sleep study with people who do that normally and see if
also the melatonin release is later and the corticosterone
rise that happens normally in the morning
also happens later. So if everything shifted, good. ANDREW HUBERMAN: OK. Yeah. There are a few
studies I've come across that really do argue
for the fact that waking up circa sunrise, that doesn't mean
at sunrise but within an hour or two, maybe three
hours of sunrise and going to sleep within
four hours after sunset or so is actually better for
the health of all human beings than is being a night owl. And the night owl,
there's almost like a night owl posse
out there, especially on social media. They get very upset when
you say that you should see morning sunlight
that after 10:00 AM, you kind of miss the boat. They get very upset,
because I think there are about 20% or
30% of people perhaps who really feel like they
function better staying up late and waking up late. And they function much
less well waking up early and going to bed early. But the data on health metrics
suggests that, sorry night owls, that they are wrong. GINA POE: Yeah, sorry me
because I'm a night owl. ANDREW HUBERMAN: Oh, boy. OK. Well, then I'm
apologizing directly. Here, I'm not a really
early morning person. I'm more typical. I wake up naturally around 6:30,
somewhere between 6:30 and 7:30 AM, go to sleep somewhere
between 10:00 and 11:00 PM. These are averages. But I do notice
that when I force myself to get up
a little earlier and go to sleep a little
earlier, that my mood and alertness and just overall
productivity is much higher. And there could be other
variables to that, too. GINA POE: You're
absolutely right. I'm a night owl. I love staying up late
at night doing you know, writing grants, writing
papers, watching movies, whatever it is. I love it. But like you and like
every human being on earth would do better if I go to bed
earlier and wake up earlier. So one good thing
for night owls is to have a child, because
they will wake you up. Their circadian
rhythms are so strong. They will wake up. And even if you
deprive them of sleep in the first half
of the night they will still wake
up like clockwork, because their circadian rhythms
are so strong at 6:00 AM. And so what you've-- you
haven't done anything good for your kid. You haven't moved their cycle
to later and be more in line with yours. In fact, you've just
sleep deprived them and made them miss a window and
made them cranky the next day and made your life
more miserable. So go to bed soon after
your kids go to bed and wake up with them. That's the way to do it. ANDREW HUBERMAN: Great. The child alarm clock, another
reason to have children. GINA POE: Yes. ANDREW HUBERMAN: I
got a dog, a puppy, and then that became a
dog, specifically, well, for many reasons. But one reason was I wanted to
be one of those early morning rides, 5:30 AM every morning. But I ended up getting a
bulldog that would literally sleep 16 hours if he could. A nuclear bomb could go off,
and he wouldn't wake up. But what I started to learn
was that Bulldogs actually have sleep apnea. As far as I know,
they're the only species that has a genetically-- they're essentially an
inbred sleep defect. And so I actually
don't encourage people to get bulldogs because
it's kind of a cruel breed. They suffer a lot in that
body that they're born into. Anyway, a dog can
accomplish some of this. But get the breed of dog that
is going to wake up early. So in other words, don't
get a bulldog or a mastiff. GINA POE: Well, interestingly,
all predatory animals like dogs, and cats,
and lions, and us-- well, more dogs, cats,
and lions, then us, well, can sleep 16 hours a day. Ferrets are predatory. ANDREW HUBERMAN: I
had a pet ferret. I used to-- and
sadly, I also used to work on ferrets,
published a number of papers, delightful animals. GINA POE: Yeah. And great because you
can study development. It's really cool,
because they're born very artricial like
we are with brains that are not very well developed. And so you can see what
happens through development and how important these
different phases of development really are. But yes, yeah, maybe we're
not as much predators as we think because in
fact, our sleep is somewhere between the prey
and the predators in terms of the amount of sleep
that we usually need a night. But those predators can sleep
16 hours, napping all day long. And they're more
crepuscular, perhaps, like their prey are, more-- ANDREW HUBERMAN: So
dawn and dusk active. GINA POE: Yeah, dawn
and dusk active. Yeah. But anyway, yes,
children and dogs-- actually, there was a poll
done by the National Sleep Foundation to see what
the number one thing is that wakes people up at night. And number two is
going to the bathroom. Number three is
children, because-- when your children are young. But that only lasts a few
years that they'll wake you up when they're babies. But the number
one thing is pets. And pets needing
to go out or cats wanting to curl up
with you or whatever it is, pets' needs
will wake you up more in the middle of the
night than anything else. ANDREW HUBERMAN: Another reason
to not get a nocturnal pet. People who get
hamsters, pretty quickly realize that they are
nocturnal, and they want to run on their wheel around. GINA POE: Yeah, you got to
put them in the living room away from where you sleep. ANDREW HUBERMAN: I vote fish
tank, folks, freshwater fish tank. There are all sorts of reasons
to not get a salt water fish tank or a child. [LAUGHS] I appreciate that vote. And I appreciate you
mentioning ferrets. And by the way, folks,
they are carnivores. They are not rodents. And they are-- they have very
elaborate brain structures. They're very smart, in the same
family as the honey badgers and the other mustelids. Anyway, I shouldn't geek out
too much on the mustelids or else I'll take the
remainder of all our time. I'd love for you to
tell us about REM sleep and the sleep later in
the night as it relates to dreams and emotionality. And this is probably the
appropriate time for you to introduce us to this
incredible structure in the brain, which is the locus
coeruleus a difficult structure to spell but a beautiful-- a
beautifully named structure. I find locus coeruleus
to be just fascinating. And I know a small
fraction of what it does. And I'm hoping you're
going to educate me and our audience more about
what it does and hopefully tell us a little bit
about its relationship to epinephrine a.k.a. adrenaline. GINA POE: Yeah. I am so glad you
brought this up, because I can totally geek
out on the locus coeruleus. ANDREW HUBERMAN: Please do. GINA POE: Locus, meaning
spot or place and coeruleus, meaning blue so you could
just call it the blue spot. That's the easiest. Every animal with a brain
has a blue spot and-- yeah, and I mean,
every other animal with a brain because
of course, there are animals with nervous
systems that are not centralized like jellyfish. But anyway, we're
digressing there. So the local coeruleus
is filled with neurons that have in them
norepinephrine which is the brain's version of
epinephrine or adrenaline, is also called noradrenaline. And what it does is,
just like adrenaline and the rest of our
bodies, it helps prime us to respond
to our environment. So when locus coeruleus neurons
fire and fire in a burst, we can switch our attention. And they will fire in a burst
if, for example, a loud noise happens in the middle of your
concentrating on something. So you can-- it
helps-- it fires. And it helps you switch
your attention to that thing and then learn quickly from it. So it's really important
in a stress response. It helps us do quick
one trial learning. And then tonic
activity during the day when you're just
doing normal going about your normal concentration
activities is really good for sustained attention. It works with the cholinergic
system of our basal forebrain which is really important
for learning and memory also to help us learn about
things and put things together. But just tonic
levels are signature of wakefulness and alertness. So too much is panic with
a locus coeruleus activity. A burst is switching attention. And then tonic levels are
sustained constant attention. And then when we go to
sleep, the locus coeruleus slows and goes from
about on average two Hertz to about one Hertz, one
cycle per second, tonically. And then when we
go into REM sleep, it's the only time when
it shuts off completely. And it appears that,
that complete silence is really, really important
for a number of things. And the main thing that I
think it's important for is the ability to erase and
break down synapses that are no longer working for us. So they encode things
that are false now, or they are encoding things
that we learned in the novelty, encoding pathway of our brain
that have now been consolidated to other pathways. And so we need to now erase
them from the novelty encoding pathway. And that is really,
really important for being able to continue to
learn things all of our lives, so like erasing
that REM or that-- what you call those, disks that
you stick into computers that-- ANDREW HUBERMAN: Hard drive-- no, thumb drives. GINA POE: Yeah, erasing
your thumb drive. So that thumb drive is what
you carry around all day long. And then during sleep, you write
that thumb drive to the cortex, to the long term
memory structures. And you need to refresh
that thumb drive. And that's what happens
during REM sleep when the locus coeruleus is
off, because whenever it's on and noradrenaline
is there, it helps us to put things together. It helps us to learn
and strengthen synapses. But it does not allow
us to actually weaken synapses that are also a really
important part for life-- important part of
lifelong learning. Yeah, so much more I
could say about that. ANDREW HUBERMAN: Yeah, locus
coeruleus sounds fascinating. So it's connected to the basal
forebrain cholinergic system. The neurons in locus
coeruleus, if I'm not mistaken, release norepinephrine,
perhaps epinephrine as well? GINA POE: Well, no, the
brain's version of epinephrine is norepinephrine. The other thing it also-- the precursor to
norepinephrine is dopamine. And so the source of
dopamine in the hippocampus seems to be the locus coeruleus. And it's still a mystery
is under what conditions the locus coeruleus
also releases dopamine. But it's really important when
we're learning something new to also release dopamine
or to at least activate the dopaminergic receptors
in our hippocampus. So yeah, so dopamine,
norepinephrine, and then there's
also galanin which is important for releasing
when we're stressed. And it helps also
without rapid learning. It works in concert
with norepinephrine and in doing what it needs to
do to strengthen synapses so that we learn really quickly. ANDREW HUBERMAN:
I love that there are multiple molecules involved,
because that signals us to a principle which is that
even if people can't remember all the names, that
rarely in biology is something handled by just
one molecule or pathway. That redundancy is the rule
because signaling attention to specific events
is so important. So that-- I'm going to
use that as just a story. I always say I wasn't
consulted at the design phase. But it makes sense to
me as to why redundancy would exist in this system. GINA POE: Absolutely. And in fact, when we form a
hypothesis about the brain, we are always wrong. And the reason why
we're always wrong is because it's more complicated
than we'd like to think. And because in our brains
when we're forming hypotheses, it's we fail to account
for all of the factors that are involved, the glia,
the neuropeptides, the neurotransmitters, the
physical structure of synapses. And so when I was going through
grad school 35 years ago, we-- the dogma was that every neuron
contains one neurotransmitter and releases one
neurotransmitter. And you had excitatory
neurotransmitters, and inhibitory
neurotransmitters, and neuro-- modulatory neurotransmitters. But that's as
complicated as it's got. And then we started talking
about neuropeptides. And people said, oh, no,
please don't complicate it. And then we started talking
about how neurons contain both neuropeptides and
neurotransmitters and maybe more than one neurotransmitter-- ANDREW HUBERMAN: Maybe
even hormones, too. GINA POE: And hormones and-- oh,
Lord, it's just so complicated. But I've got to admit
that's why it works, right? And every time the brain teaches
us something new about itself that we didn't
hypothesize, we say, oh, of course, that wouldn't
work if the way I hypothesized it-- with it. We actually need redundancy. We need all of these
systems to work together. ANDREW HUBERMAN: Yeah. It's daunting
sometimes, but it also insures many careers in science
and neuroscience in particular. So note that
aspiring scientists, there's plenty of
room for discovery. GINA POE: Do you want me to
talk about norepinephrine-- ANDREW HUBERMAN: Yeah. So what-- GINA POE: Emotion and-- ANDREW HUBERMAN: Yes. Well, what I'd love-- what
I'd love for you to tell us about is what role this
lack of norepinephrine release during rapid eye movement
sleep is thought to achieve? And maybe you can also
review some of your work, describing conditions under
which norepinephrine invades-- GINA POE: Yeah, invade sleep. ANDREW HUBERMAN:
Rapid eye movement sleep and other
patterns of sleep and how that can be detrimental. GINA POE: Yeah. So a lot of this is
hypothetical but based on a lot of good evidence
that we're sewing together into a schema from which
these hypotheses come, so a model schema from
which the hypotheses come. But one thing that
happens to people with post-traumatic
stress disorder is that there is
a lot of evidence that the locus coeruleus doesn't
stop firing in REM sleep. So-- whereas their
levels of norepinephrine might be similar to
people without PTSD during the day and even during
the first part of the night, during the wee hours
of the morning. And when you measure
norepinephrine levels from metabolites in the blood
or the cerebrospinal fluid, you see that people
with PTSD, it's during the wee
hours of the morning when you have the most
REM sleep that they have their norepinephrine levels
differentiate most from those that don't have PTSD. And so that's evidence that
the locus coeruleus is not shutting down during REM
sleep like it should. Other evidence is
heart rate variability. When our locus
coeruleus is firing, our heart rates are
generally a little higher. And they don't vary
as much as they do when the locus
coeruleus is not firing. So during slow wave
sleep, normally, have this big, juicy variability
in heart rate with every breath in and breath out because
our noradrenergic levels or norepinephrine levels are
lower during REM sleep that goes away entirely. And our heart rate is dominated
by parasympathetic rather than sympathetic activity and also
what our brain is driving, what our dreaming about. For example, if we're
dreaming we're running, our heart rates will go up. But norepinephrine levels
still should be low or off. So people with PTSD that
noradrenergic's we're studying these in
rats, too, is it true that our locus coeruleus
doesn't shut off when we have post-traumatic
stress disorder? And the preliminary
evidence is yes, it's true that it doesn't shut off. So what that would do
is norepinephrine would act at synapses to prevent
that weakening that you really need for example of novelty
encoding structures. And it keeps memories in that
novelty encoding structure even once it's consolidated
to the rest of the brain. So in the hippocampus which
is important for remembering things throughout our lives
and it's that thumb drive, we need it to be
erased so that we can learn new things once
it's been consolidated to the hard drive of our cortex. And so if we're not
able to do that, we fill up that
RAM really quickly or that thumb drive
really quickly, and we're not able
to learn new things. So for example,
after a trauma, I talked about the locus
coeruleus responding in stressful situations. That's great. It's very adaptive. But then you need it to stop. Once you've learned what
you need to learn from it and you want to go to
sleep, you need the locus coeruleus to calm down. And during REM sleep,
you want it to stop, because then when
you consolidated that traumatic
memory to the cortex, you need to erase it from the
novelty encoding structures, for example, in the
hippocampus so that then when you're in the context
of safety, you can learn those new
things, those new contexts and stop responding
to those same stimuli as though you're in
that original situation. So if you're not able to
erase that thumb drive, you will always feel
like that trauma happened that same day,
earlier that same day and respond as you
would to an early-- a recent trauma which is with
beating heart and all of that. So even memories
that are years past, if you're never able to
downscale that novelty encoding structure and purge it
from that traumatic memory, it will stay fresh, and new,
and then become maladaptive. ANDREW HUBERMAN: I'd like
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Inside Trackers plans. Again, that's
insidetracker.com/huberman to get 20% off. What approaches are
you aware of that can turn down the output
of locus coeruleus during these phases of sleep? And for that matter,
what things can cause ramping up
of locus coeruleus during this phase of sleep? We've had a couple of podcast
episodes, solo episodes and with guests
talking about trauma. We had Dr. Paul Conti who's
a Stanford trained, Harvard trained psychiatrist who
talked a lot about trauma wrote an excellent
book on trauma and certainly sleep was
emphasized as a key thing like get enough sleep. But here, you're saying
even if somebody with trauma gets enough sleep,
if locus coeruleus is hyperactive during sleep, those
traumas are going to persist. And most of the trauma
treatments that I'm aware of are everything ranging from
cognitive behavioral therapy, talk therapy, drug
therapy, EMDR, hypnosis. Nowadays, there's a lot
of interest and attention on clinical studies on exploring
psychedelics, high dose psilocybin, and MDMA. So it's a vast landscape, none
of which, as far as I know, is really focused on
sleep specifically. GINA POE: No, they're not. And they should be, because
actually, psychedelics is a sleep like state. And it's a REM sleep like state. Although of course, there
are some major differences. So yeah, so much
to talk about here. So antidepressants are often
noradrenergic or serotonergic reuptake inhibitors. So they leave
norepinephrine actually out there in the synapses. And what that does is
it inhibits REM sleep. And if you're able
to get REM sleep, it would probably
be REM sleep with some noradrenergic activity. So actually, I think-- anyway, I'm not a physician--
that antidepressants are counter indicated. You don't want to take them
if you've experienced a trauma and you're experiencing
PTSD, because if anything, it's going to make
it worse or at least prevent the type of
adaptive REM sleep that you really need in order
to resolve those emotions and move on. ANDREW HUBERMAN:
Is that statement specific to
antidepressants that tickle the noradrenergic pathway? So the one that
comes to mind is-- can never pronounce it,
buproprion, which is what-- I think brand name
is Wellbutrin. It's a dopaminergic and
noradrenergic agonist. So that's the net
effect as opposed to the Prozac, Zoloft
variety which are SSRIs. GINA POE: Yes, yes. But SSRIs themselves
also are problematic, because-- we didn't
talk about it yet, but the dorsal
raphe nucleus which produces serotonin which
specific serotonin-- specific serotonin reuptake inhibitors
block from being reuptake and leaves too much
serotonin out there. And what serotonin also is
another noradrenergic-- sorry, another neurotransmitter that's
downregulated during REM sleep. That's specifically
off during REM sleep. And what serotonin does is it
weights all of our cognition to being able to
recognize novelty again. So it weights our brain away
from a sense of familiarity and toward novelty. And it might be
one reason why it's an effective antidepressant
because it makes the world feel fresh and new again, right? But you-- when you
have too much, you're holding a novel traumatic
memory in your novelty encoding structure too
strongly already, you don't want to, again, weight
things toward novelty. You need that
absence of serotonin also to help you get
that sense of familiarity and to start erasing the
novelty encoding structures. So you need both to be absent. ANDREW HUBERMAN: It's
really interesting. We hear a lot about serotonin. And it's not often discussed in
terms of its features related to novelty enough I think. And what you just described
cues me to something that Dr. Paul Conti and others
have said in terms of trauma. And here, I'm paraphrasing,
so my apologies to them for not getting
this exactly right, that an effective
treatment for trauma does not erase the
traumatic memory. But it causes a transition
of what once was disturbing, and invasive, and maladaptive
to eventually just become a boring old story that has
a fuzzy texture to it as opposed to this sharp
high friction texture that invades our thinking
and obviously, our sleeping states as well. So again, and I
appreciate the disclaimer, the caveats around not being
a clinician, et cetera. But I do think that there's
a lot of interest now in whether or not
antidepressants are effective for trauma or not. And I think these aspects
of neuromodulation as they relate to, let's call
it, erasing traumas or changing the emotional load of
traumas during sleep is something important
to take note. We also have a lot of clinicians
that listen to this podcast. So they should also
take note, please. So if I want to reduce the
amount of norepinephrine released from locus coeruleus
during rapid eye movement sleep to eliminate the troubling or
maybe even traumatic memories and allow late stages of
sleep each night to have their maximum positive
effect, is there anything that I can do besides avoiding-- avoiding traumas, avoiding
serotonergic or noradrenergic compounds? GINA POE: Well, I would also
avoid anything just prior to going to sleep that
might excite those systems, so a lot of novelty, a
lot of the exciting stress inducing video games. Try and enter sleep with
as much calm as you can, so maybe deep
breathing exercises. That's a beautiful way to
calm your sympathetic fight or flight system
is deep breathing. And we haven't been able
to test this with rats because we can't ask them to
do a deep breathing exercise. There might be a
way we can do that. But I haven't found out
or figured it out yet. But if there's a way you can
make your sympathetic system, nervous system calm down
before you go to sleep, might free for you
meditation, or deep breathing exercises might be
for some, a warm bath, or a comforting book, nothing
too exciting but also nothing too boring, perhaps,
just something right in the middle which
makes you feel happy and calm is what you should do. And if you instead go to
sleep while you're anxious or you're hyped up, then your
sleep could become maladaptive. Another thing that happens
in rats that we have yet to know if it
happens in women is that female rats have three
phases of their estrus cycle that their locus coeruleus
doesn't seem to calm down during REM sleep as much. And we don't know why, but
during the high estrogen phases of their estrus cycle, the
locus coeruleus shuts down just like it does in male rats. But in the other three
phases, it doesn't. So one thing that might
work and in fact, there are a few studies that show
it could work really well is giving women
after a trauma event, something that
contains estrogen, because estrogen somehow
is protective against PTSD. And they know that through
a retrospective studies, where they gave women in
emergency room either a pill with estrogen and/or without. And those that had the
pill with estrogen in it were much less likely to
get PTSD from that trauma as measured a year
later than those that had the pill without. So there's really good
studies by Bronwyn Graham-- she's out of Australia--
to really hone in on how much estrogen do you
need and also testosterone just so you know, gets converted
to estrogen in the brain. So testosterone also
can be protective, because it gets
converted to estrogen. But there's something
about estrogen that's really helpful
and protective about from the high
locus coeruleus firing. And this is, again, preliminary
data that we don't have full-- we don't have all
the answers yet. And we are looking into
it actively right now. But it's really important. The other thing about
women is that we are two to four times more
susceptible to anxiety related mental health disorders
including post-traumatic stress disorder. So if we could figure out what's
happening to locus coeruleus during sleep in women
and then figure out a way to normalize that so the
locus coeruleus is silent when it needs to
be silent, I think we could go a long
way in helping women be more resilient to
stress related disorders. ANDREW HUBERMAN: What are
some other sex differences as they relate to sleep? GINA POE: Yeah. That's a really good question. There have been very few
studies, unfortunately, of women and sleep, women and
estrus cycle or menstrual cycle and sleep. But what we have found which
actually largely replicated a study in 1960 is
that women or females rather at high estrogen,
high hormonal phases of their estrus cycle
or menstrual cycle sleep a lot less. But that sleep is
more efficient. So that sleep is more dense
in those sleep spindles, which I haven't gone into
what they might do except this connection
between the hippocampus and cortex. But those sleep spindles are
more dense and more coherent across the brain areas. The theta cycle which
is 5 to 10 Hertz in the hippocampus important
for one-year learning and also important
during REM sleep is also bigger
and juicier during the high hormonal phases. So even though
there's less sleep, it's more efficient and better. So all of that efficiency
seems to be reduced in those other hormonal phases. So even though you might
sleep a little more, you might need more
sleep, in fact, in order to accomplish
the same thing that you can get with that short
very efficient sleep of high hormonal phases. ANDREW HUBERMAN:
Very interesting. I think there is
a growing trend, at least among NIH-funded
grants to require that as they refer to it in
the grants of biological sex as a variable. And here, we're
talking-- nothing here about sex, the
verb, although, I'm sure there are studies
about that, too. But biological
sex is a variable, because there is a dearth
of studies exploring sex differences in most everything. There are all sorts
of reasons for that. But more importantly
that fortunately, the trend is shifting. GINA POE: Yeah. And even when you study males
versus females, a lot of people just say include
females in their studies but then don't track the estrus
cycle or menstrual cycle. And hormones have huge
effects on our behavior. Just think about-- when you said
sex before our hormones come in, we're not interested in it. And suddenly, that's kind of
a main driver of behaviors. Hormones can definitely change
who we are and what we do. So we should be studying
hormones not just sex. ANDREW HUBERMAN: I always
say that puberty is perhaps the most massive
transformation and rate of aging that any of us go
through in a short amount of time. An individual, their
cognition changes. Their worldview changes. And that's largely
hormonal-driven. And obviously, neural
architectures change, too. I'm very happy that
you mentioned-- I'm trying to get
into calmer states prior to sleep and
some ways to do that. I'm a big fan and I've talked
a lot before on this podcast about things like yoga nidra
which is a non-movement based practice, sometimes called
non-sleep depressed where people actually take some
time each day to practice how to go into a more
parasympathetic a.k.a relaxed state deliberately, because
it's a bit of a skill. GINA POE: Yeah. ANDREW HUBERMAN: It's-- and
there there's some good data really, mostly out of a
laboratory in Scandinavia showing huge increases in
nigrostriatal dopamine when people go-- basically, engage in a practice
of deliberate non-movement and that the brain
actually enters states of a very shallow sleep. So it's sort of nap-ish. But the idea is to actually
stay awake but motionless. And it does seem to restore
a certain number of features of neurochemistry. But perhaps more
importantly, it teaches people to relax which is
something that most people are not very good at. But in any event-- and people who listen
to this podcast have heard me say this
over and over again, so I sound like a broken
record, but this practice as a zero cost practice
that doesn't require any pharmacology does seem to
really enhance people's ability to fall asleep more
quickly and to fall back asleep if they wake up in
the middle of the night. So in any event, another
plug for NSDR, yoga nidra. GINA POE: Well, I
just also want to add to that, that's one of
the reasons why insomnia is so insidious is because when
people feel like they haven't gotten enough sleep, and they're
not getting enough sleep, and they become anxious
about getting enough sleep, and then they're anxious
before going to sleep, like I'm not going
to fall asleep, it's going to be 45
minutes, and then that's a positive feedback loop. So you need to break
that loop, say, OK, my body is going to get
as much sleep as it needs, I needn't worry about it, and
then practice this relaxation to say, hey it's all OK,
it's going to be all right, and then concentrate on
things that relax you, whether it's
concentrating or not concentrating, whatever it is. You mentioned yoga nidra. And that reminded me of
transcendental meditation which is something that also
hasn't been studied well, largely because we can't ask
nonhuman animals to do it. And so we don't know
what's happening with our neurochemistry
and our brain activity in a deep and meaningful way. But one thing that
has been shown in those that can
do it really well is that, that theta
activity that I said happens when you're
learning something or when you're in REM
sleep, it's well established and increases during the
transcendental meditation. So it might be that some
states of meditation could in some ways
replace or mimic some functions of, for
example, REM sleep. But again, we don't know
if all the neurochemistry is right to do, for example, the
thing that I was talking about, which is erasing the
novelty encoding structures of the brain. That needs an absence of
norepinephrine and serotonin, which we don't know
if that goes away with transcendental meditation. We just don't know the
answer to that yet. ANDREW HUBERMAN: Yeah. The studies on yoga nidra
and sleep replacement are interesting. It does seem to be the case
that nothing can really replace sleep except sleep. But that if one
is sleep deprived or is having trouble
falling back asleep that these things like-- and I hear it's-- I acknowledge this is
essentially like yoga nidra, but we now call it
non-sleep deep rest or NSDR, because oftentimes, for
names like yoga nidra act as a barrier for what
would otherwise be people willing to try a practice. It sounds mystical. GINA POE: --and yoga. ANDREW HUBERMAN: It sounds
like flying carpets. And it sounds like you
have to go to Esalen. By the way, Esalen
is a beautiful place. But it sounds like you have to
go there or live in the West Coast to believe in this stuff. But it's simply not the case. These are practices
that are really just self-directed relaxation
as a practice that allows people to get better and better
at directing their brain states towards more relaxation. And most people
have an asymmetry. Like for instance,
most people can force themselves to stay up later. But they have a hard time
going to sleep earlier. And that just speaks
to the asymmetry that's probably adaptive
in survival-based that we can ramp ourselves up
far more easily than we can tend to calm ourselves down. GINA POE: Yeah. And actually to appeal to
other Christians like me, prayer can be a wonderful
way to calm yourself down, because through prayer you're
giving your carries to God and saying-- and then you are
relaxed, more relaxed. And I just want to say that
because, the same reason that yoga might put
some people off. It might put some people
off to talk about prayer, but it's the same process of
being able to relax, and yeah. ANDREW HUBERMAN: And get
outside our own experience a little bit. GINA POE: Yeah. Back out get a world
view that might actually also help us to relax. ANDREW HUBERMAN: Well,
you might be surprised at how many clinicians
and scientists who've come on this podcast have
mentioned things like prayer from various perspectives,
Christianity, Judaism, Muslim traditions,
and others that-- as a parallel to
all of these things. And I think what it speaks to
is the fact that, ultimately, the biological architectures
that we're all contending with are going to be
identical, right? And so different ways to
tap into them and ones that are congruent with people's
beliefs, I think are great. GINA POE: Yeah,
because anything, non-congruent with your
beliefs is also stressful. ANDREW HUBERMAN:
And feels forced. And that's why this
idea of calling it non-sleep deep rest in
addition to yoga nidra was not to detract from
the naming or the history around yoga nidra. But I was finding
that it was a barrier. Likewise, yoga nidra tends to
include things like intentions whereas NSDR scripts. And by the way, we will provide
links to some NSDRs and yoga nidra scripts. But NSDR has no intentions. It's simply a body scan
deep relaxation-based. So it's the scientific
version of all of this stuff. And actually, we study
it in the laboratory and some of the brain
states that people go into. But that's a discussion
for another time. GINA POE: This is hard not to-- My mother used to tell
me when I would complain, I can't go to sleep, she'd
say, well, start with your toes and relax. So you would clench your
muscles around your toes then relax them and do that
all the way from your toes all the way to your head. And I don't know
where she got this, it might have been
her own common sense or she might have gotten
it from this NPR shows called The Mind Can Keep You
Well she used to listen to. But that's another
intentional relaxation that focuses on the
body rather than on your own mental
processes, but. ANDREW HUBERMAN: I do a little
bit of work with the military. And there's a method
within certain communities of Special Operations
in the US military, where if they can't sleep
or they're having challenges sleeping, they will
deliberately try and relax their facial muscles in
particular like drape the facial muscles
and use long or exhale emphasized breathing
does seem to increase the probability of
transitioning back into sleep. And those are hallmarks of yoga
nidra, non-sleep deep rest, body scans. And so I think all
of these things converge on a common theme. As neurobiologist, we can
say, all of the things that we are describing
certainly move the needle away from locus coeruleus activation. And we haven't
done the experiment to really look at that. But it seems all these things
are counter to noradrenaline release. GINA POE: Right. Another one is yawning. Yawning in itself
is, in fact, kind of tensing of all the
muscles in your face and then relaxing them. So it might be why we yawn. We don't know why we yawn yet. But it might also-- it
would be really great. Actually, animals yawn, too. ANDREW HUBERMAN: My bulldog
was a-- perpetually. If he wasn't sleeping,
he was yawning. GINA POE: And it would be
interesting to see what yawning does to the locus coeruleus. Does that also calm and switch
the locus coeruleus activity, because it's an interesting
that facial nerve like trigeminal nerve
through the vagus connects indirectly
to the locus coeruleus and has a powerful
effect on that. ANDREW HUBERMAN: Interesting. A common, I think friend of ours
and direct colleague of yours, Jack Feldman was a guest
on this podcast telling us about all the amazing structures
he and others have discovered in respiration and breathing. It sounds like we
have a collaboration brewing the three of us
should definitely carry out. I'd love for you to share
with us a little bit more about the spindles that
have come up a few times. And I don't know if
it's relevant to this. So if it's not, let's
separate it out. But I'd love for you
to tell us a little bit about the role of sleep in
problem solving and creativity. And if spindles are
involved, then I'll consider myself lucky
for batching them in the same question. And if they're not
involved, simply feel free to separate them out. GINA POE: I think they
could be involved. And the reason why
I think they could be involved because we now
know a lot more about spindles. First of all, the first
thing that we knew-- first of all, we ignored them. Then we thought
they had something to do with keeping us asleep. And that was their function is
when an external stimulus came, they would keep us asleep
because they would arise. But now, we know that
the density of our sleep spindles, the number that
we produce per minute is well correlated
with our intelligence in the first place
and that no matter what your intelligence is and no
matter what your sleep spindle density is, if you're learning
something during the day and increase your
sleep spindle density, it's really almost perfectly
correlated with our ability to consolidate that
information and incorporate it into the schema that we
already have in our brain. So if you try and
learn something new, even if your sleep spindle
density at baseline is great, if you don't increase
your sleep spindles that night, you're not going to use
sleep to really incorporate. Interestingly,
sleep spindles are poor in those with
schizophrenia. It's one of the
characteristic signatures of sleep is that sleep spindles
are very few and far between, which might mean that
people with schizophrenia might not be able to incorporate
new information into already existing schema. And instead, it flaps
in the breeze out there and can be accessed
erroneously at times when you don't want it to be involved. So I digress, so sleep
spindles and creativity. So one of the things we now
through some great studies by Julie Seibt and Anita
Lüthi is that sleep spindles are accompanied by an
incredible plasticity out in the distal
dendrites, the listening branches of our neurons that
listen to other cortical areas. So there are proximal
dendrites in our neurons that listen to
the external world and are conducted
through the thalamus. And then there are
distal dendrites which listen to an internal
conversation that's happening in our brains. It's kind of our
internal state, really. And during sleep
spindles, that's when those distal dendrites
are able to best learn from other cortical areas
and from the hippocampus. It is during sleep spindles that
the hippocampus and the cortex are best connected and when
that incredible plasticity can happen. When I talk about schema, that's
a cortical, cortical thing. That's when the image of
Santa Claus and presents comes together. It's not through
some external thing. Once we learn those
things together, it's our cortex that
encodes that and brings those images back up together. And that's during
sleep spindles when that's happening, when that-- there's big surges of calcium
into those distal dendrites, and where plasticity happens
in just huge amounts. During that sleep spindle stage
of sleep which is N2 stage, there's also another
excitatory event that comes all the
way from the brainstem and projects everywhere
in our cortex which is called PGO waves. That's P for pons, G
for geniculo nucleus of the thalamus which is where
they're first discovered, and O for occipital
area which is our visual area which is, again,
where they're first discovered. But in fact, it's now been shown
that PGO waves, which we should generalize to P waves because
they come from the pons and go to the thalamus
and then the cortex, happens all over the brains. And that is where glutamate,
which is a major excitatory neurotransmitter involved
in learning and plasticity is being released
in big amounts, also in those distal dendrites. So P waves and
spindles work together to cause plasticity and
sew our schema together which could be the origins
for insight and creativity. Now, when PGO waves or P
waves were first discovered, it was thought to be random,
because this small area that generates P waves
all over the brain projects all over the thalamus
and causes P waves all over. And you don't measure P
waves all over the brain at the same time. In fact, it's just seems
sporadic and random. So that's probably-- and P
waves also happening even more during REM sleep, rapid
eye movement sleep. So that's why people
think that REM dreams are so random is because
these P waves are random. And they could generate
dreams because they're an internal source of excitation
that replaces the outside world during our dream state. And so these P waves, if they
are random, could function-- could be the
underlying reason why REM sleep dreams are random. And it might also be why
creativity can happen there because we're
randomly activating-- co-activating different
things in our brain that we can then sew together. But it might not be
as random as we think. So that's the caveat there. ANDREW HUBERMAN: I just
learned a lot from you, because I teach brain
stem to medical students. And I talk about the pons. And the pons is like
this dense collection of all these different
nuclei involved in a bunch of different things. And it's close by a bunch
of interesting things. And it's still a
mysterious brain area. But when I learned
about PGO waves, I thought
pons-geniculo-occipital, because occipital is
most commonly associated with visual cortex,
I thought it was the origin of the visual
component of dreams. GINA POE: And probably is. ANDREW HUBERMAN: I'm
very happy to learn that they should be called P
waves, because they include lots of different
areas of the brain. And it makes really
good sense to me why the pseudo
randomness of dreams especially these late
night and early morning-- later in sleep I should say
and early morning dreams seem to be cobbled together
from disparate experiences. You walk through a
door and suddenly, it's a completely different
context and landscape. GINA POE: Yes,
beautiful. beautiful. ANDREW HUBERMAN: I
like this idea a lot. It makes intuitive sense
it makes biological sense. It also gives me
something to talk about to the medical
students next quarter when I talk about pons. GINA POE: Right. You want to talk about
where in the pons, it's right below
the locus coeruleus. It's called the sub coeruleus. They're glutamatergic. It's also called SLD, sub
lateral dorsal nucleus, so. ANDREW HUBERMAN: So note to
any aspiring neurobiologist, there's a vast landscape of yet
to be undiscovered structure and functions in the pons. You want to work
on something that is sure to reveal something
novel, work on the pons because it's in every textbook. It's clinically very
important structure. Sadly, gliomas and other cancers
of the brain can sometimes-- can often surface in the pons. But we still know
very little about it. I read a paper this
last year or-- and I think it was covered in
a bit of popular press, that during rapid
eye movement sleep, people can solve problems or
respond to external stimuli. For instance, they would
give them math problems. They'd whisper in their
ear while they were in REM sleep, what's 2 plus 2. And then people would say, even
though they were paralyzed, apparently they could
still move their mouth, because they'd say four
or something like that. Or they'd say, what's your name. And people could respond. And so that in REM
sleep, perhaps, people-- some elements of cognition
are still active. GINA POE: I'm glad
you brought that up. ANDREW HUBERMAN: What
are you thinking-- and I don't know the
authors of that study and-- listen, if ever I
say something wrong, it's great on this podcast
because someone will tell us in the YouTube comments. It's one of the great
uses of YouTube comments. But I'd love to know your
thoughts on that study. Is that just kind of an
odd feature that or does this have meaning. Should we actually
care about this result? GINA POE: There is
no just about it. It's really actually
intriguing and interesting and might relate to
this paper that I talked about where we said
different areas of the brain can be in different
states at the same time. So lucid dreaming
is another thing we can't ask animals
to do or can't ask them if they've done it. But we can certainly
ask humans to do it. And some people can
do it really well. And it would be really
interesting to see in those people who could lucid
dream really well whether they spend more or less time
in this asymmetrical state where one area of the
brain is in one state and another area of the
brain is in another. And it might be that those
people can respond to questions during REM sleep. Best are those that have the
most asymmetry or dissimilarity or dissociation between
subcortical and cortical structures. Or it might be that they're the
ones with the most symmetry, we don't know. I do worry a little bit
about lucid dreaming, because people are-- it's a fad. People are really
excited about it. And to be able to
remember one's dreams is fun often unless
there are nightmares. But it's really interesting. Or to be able to direct one's
dreams if they are a nightmare is really a wonderful
power to have, to be able to redirect
a nightmare that has been repeated
to something else and then kick
yourself out of that. Repetitive nightmare
is really nice. But I worry a
little bit about it, because we know so
little about what's actually going on in the brain. And if this lucid dreaming
state is preventing us from, for example, from the
locus coeruleus from calming down or the serotonergic system
from silencing like it should, and maybe what we're
doing during this state is Yeah we're activating the
learning and memory structures but in a way that's maladaptive
in terms of the erasure that we need to do. So maybe one of the reasons
why most people don't remember most of their
dreams is for good reason. Your hippocampus
is in a state where it's not writing new memories. In fact, it's writing out
its-- the memories it learned during the day to the cortex. And it's immune from
incoming new information. So maybe lucid dreaming
is bad, because you're activating the hippocampus
in a way that's writing new memories. And it might be
really maladaptive for things like PTSD. On the other hand, let me just
argue myself right out of this, when I used to have a repeated
nightmare when I was a kid, my mother who was so wise would
tell me, well, listen, just-- next time you're in that
dream, say, hey, I'm in a dream and then change
something about it. So she and I rehearsed
what the horrible dream that it was, big
monster running after me. And my legs were like mud,
and I couldn't run away. And it was just terrifying. And that was a dream I would
have time and time again. She said, OK, next
time what are you going to do when that
monster comes after you? I'm going to run away. No, that's what
you do every time. And it's always
the same outcome. You can't run. So let's do something different. What could you do
that's different? So I came up with all-- I could turn around and
punch it in the nose. Yeah, that's great. And so the next time
I had that dream-- I did recognize this is
that same old dream which means that there's
part of my brain that's conscious enough to know
that I'm in a dreaming state. And then I didn't have
the courage in my dream because I was still
terrified to punch or touch the monster in any way. But I did have the
courage to turn around and look it in the
eye and say no. That was enough. I said no. And that was enough to knock me
out of that rut of that dream so that I never had it again. I never had that
same dream again. And in fact, it gave me
peace about dreaming, because I knew
that if ever there was a nightmare that
was just too scary, I could probably do something to
change it and knock myself out of it. So even though, I don't
recommend lucid dreaming on a normal day-to-day basis, if
it's enough that can knock you out of a rut-- one thing that happens
with people with PTSD is they have the same repeated
horrible nightmare which is often a reliving of
the days trauma that had. So maybe lucid dreaming
can be used on occasion to be a powerful tool, because
there's so much plasticity that happens during REM
sleep to knock you out of that rut of reliving that
event and just change it. And you could probably practice
that during wakefulness, rehearse the event that
happened that was so traumatic and then just introduce a new
element like, now, I'm safe. Now, the sound that was
associated with that really traumatic thing, I should now
associate with something else. And the next time
I have that dream, I'm going to change it
so that sound is now this new thing that it should
be associated with safety. And that might be
enough, maybe, I hope, to knock you out of
that repeated nightmare and maybe even start you
on the path to recovery, because if you can calm
down about those nightmare states of sleep, then maybe
your local coeruleus which is involved in stress
can also relax. And you can do the erasure
parts that need to be done. ANDREW HUBERMAN: I love it. I seem to recall a paper-- and I'll have to find the
reference and send it to you, we will also put in the
show note captions-- that described a protocol
essentially matches this idea. And I think what they had people
do was either cue themselves to a particular smell
or tone in wakefulness then to try and recall
a recurring nightmare. Then during the
night sleep, they had the tone playing in the
background which would then cue them to the wakeful
state-- they're still asleep, mind you, but in the pseudo
lucid or lucid state, and then try and change some
variable as you're describing. Some either look the
predator in the eyes or do something different. And then in the waking state,
take a little bit of time to try and script out a
different narrative altogether. And it took several
nights, as I recall, or more but that they were
able to escape this recurring nightmare. GINA POE: It's like a
week or something, yeah. ANDREW HUBERMAN: So you're
familiar with the study? GINA POE: That's
a beautiful study. I loved it. ANDREW HUBERMAN: Yeah, we
will put a reference to that. I need to revisit that study. It was pretty recent, but I
need to dive into it again, because I think I didn't go as
deep into it as I should have. GINA POE: No, no but the
one thing that you-- you said many right things. But one of the
things you said is that they were able to cue the
dreamer when they knew-- when they were going to REM sleep. And then they played the
sound or had the odor. Now, when you're normally
asleep alone in your bed, you're not going to be
able to cue yourself. But it might be that rehearsal
enough before you go to sleep is enough to help cue you
to that repeated nightmare, remembering what the nightmare
is and then figuring out how to cue yourself to
do something different. ANDREW HUBERMAN:
For years, I had the same recurring nightmare
over, and over, and over again. And it was so
salient and so clear. And I'm not going to share
what it is, because it's not that it's that disturbing. It was just-- I think it was the
emotional load of it and just how salient
certain features were, like one person who's
a real life person had a particular clothing on. And it's like, and that
just served as this cue. And I don't know if I ever did
any direct work to try and deal with it. But now, it almost seems
silly to describe it. GINA POE: Oh, yeah. Well, dreams are usually
silly to describe. ANDREW HUBERMAN:
It pretty silly. But it was a pretty
violent dream. GINA POE: Yeah. And your emotional
system is so geared up during REM sleep
which is another thing we could talk about. ANDREW HUBERMAN: Yeah, please. I would love to. Yeah, so locus coeruleus
is ideally suppressed. So we can't release
norepinephrine. We can't act out our dreams
during these very emotionally laden thoughts and
storylines during sleep. This almost starts to sound
like a little bit of a built in while sleeping
trauma therapy, because most trauma
therapies involved trying to get people
into states of counter to what most people
think you actually want to get close to the trauma
in terms of the narrative or try and suppress the
emotional activity of it or-- I guess that's the motivation
for ketamine-based therapies for trauma-- or I've also heard, and this
is still perplexing to me, that other waking-based
trauma therapies involve taking people the other way,
making it very cathartic, take them to the peak of
the emotional response but then allow that
to finally cycle down into a more relaxed response. So please, if there's
anything about locus coeruleus and dreams and that can help
people basically extinguish traumas or traumatic
features to real life events, we definitely want
to know about them. GINA POE: Yeah. Well, I think one of
the things that people thought might help after a
trauma like a school shooting or whatever, car accident,
is to talk about it. But in fact that ended up
being counterproductive. And I think one of the reasons
why it was counterproductive is because it didn't
take them back down. It brought them up and
continued to reactivate the emotions of
it but then didn't emphasize the safety of
the fact that it's over or help them work through
how they might avoid it again in the future to calm the
sympathetic nervous system down again before they went to sleep. And none of these studies has
sleep ever been considered. But to me, that's the key
part, is bringing down your sympathetic nervous
system before you go to sleep so that your
sleep can be adaptive, your locus release can
shut off like it normally does or should do and then able
to erase the novelty of it. The other thing that I
just mentioned a minute ago was that the emotional system is
highly activated in REM sleep. And that's definitely true. And that might seem
counterproductive in terms of the
nightmares and how to help REM sleep be
a therapeutic thing rather than reinforcing the
emotionality of the trauma. And I think the key
to that again is the absence of norepinephrine. So even though the emotional
system is in high gear, without norepinephrine,
you can actually divorce those highly
activated emotions from the cognitive
parts of the memory that you have just written
out in that N2 stage of sleep when the sleep
spindles are going. So you've just now
consolidated the information that you'll need to survive
and to make that adaptive. And now, you need to
divorce from that schema and from that semantic parts
of memory, the emotional part, because whenever you
remember something, it's fine if you remember the
being emotional at the time. But you don't want to bring
back and sew into that memory all of the same
emotional systems. You don't want to bring
back the heart rate changes, and the
sweating, and all of that. You want to be able to
remember all the parts of it and even remember that
you were traumatized and that you did cry
and that you did have-- your heart was racing. But when you're talking
about it years later, you don't want to have to
relive all that, otherwise who would ever want to recall a
traumatic memory because you're basically putting yourself
through the same trauma which is what people with PTSD have. They don't want to recall
this traumatic memory, because it's reliving it. Like it's just happening again. So that's what we're thinking
is that the emotional parts are no longer-- are not
able to be divorced because the norepinephrine
system is not downscaled during REM sleep. And so that REM sleep serves to
instead reinforce and in fact amplify the emotions because
your emotional system is up, locus coeruleus
is high, re-sewing in every night the
emotionality of those memories and with the memory itself. ANDREW HUBERMAN: You've told
us a lot about locus coeruleus and norepinephrine
from locus coeruleus. Is there any role for
norepinephrine, epinephrine, and cortisol released
from the adrenals? My understanding is that
norepinephrine and epinephrine will not cross the blood brain
barrier which is probably why we have a brain-based
noradrenergic system, locus coeruleus,
and other neurons. Actually, that's a
question I should ask you. Are there other
sites in the brain where norepinephrine
is released from or is it just locus coeruleus? GINA POE: So there are seven,
nine different adrenergic. Yes, there's nine different
adrenergic structures. ANDREW HUBERMAN: I'm
sorry I didn't ask. But it just occurred to me that
in some cases like with raphe, there are other sources
of serotonergic drive in the brain. But raphe is like the main side. GINA POE: Yeah, that's the
one that goes to the cortex and the locus coeruleus
is also the one that goes to the cortex. But there are other adrenergic
sources, some that-- from the brainstem that descend
and help us to ignore pain, for example, when we're
stressed and needing to run away from the tiger, right? We don't want to be
thinking, oh, my ankle hurts. You want to just be
able to ignore it and go do what you need to do. So yeah, so there are lots of
other noradrenergic nuclei. But the locus coeruleus
is the main one that projects all over the brain. Actually, the only place
that doesn't project is the dorsal striatum. You talked about ventral
striatum and addiction. The dorsal striatum
is the only place the locus coeruleus
doesn't project to. And that's involved in
procedural learning and motor learning, kinds of
learning that take over when your hippocampus, for
example, is compromised. Bilateral, if you don't
have good hippocampus, you can still do procedural
learning and do-- and it's great. It's a redundant system. And so if your locus
coeruleus is not working, if you don't have it
anymore, you can still do a-- if you don't have
a good hippocampus, you can still do learning
through this dorsal striatum on the structure. So it might be for those
kinds of learning functions, sleep deprivation
where you never let the locus coeruleus
stop firing is OK, because it doesn't have any
receptors for norepinephrine anyway. So yeah. ANDREW HUBERMAN: And what
about bodily like adrenals. I often remind people there's no
such thing as adrenal burnout, per se, that adrenals
don't actually burn out. But some people have adrenal
insufficiency syndrome. Other people have
adrenals that are just chronically cranking out
epinephrine, norepinephrine, and cortisol at the wrong
times in particular. GINA POE: Yeah. So that-- those are
great questions. And I think the answers
to them have yet to be discovered,
the connections between our periphery and
our central nervous system. But we know that there
are beautiful connections. And it's untapped
source of being able to manipulate our brains
is to work through our bodies. And so our adrenals
do great things. They constrict
our blood vessels, causing higher blood pressure
which helps blood rush out to all the extremities that need
blood, our muscles for example, for running away from
the lion, or the tiger-- ANDREW HUBERMAN: Or
meeting a grant deadline or catching a train. GINA POE: Or catching
a train, yeah. The adrenals help our
hearts pump faster. Our muscles get perfused
with the blood it needs. It diverts blood
and everything away from our parasympathetic system
which is rest and digest. We don't really need to
digest that croissant when we're running for a train. We can do that later. So it's doing really
important things. What we don't know, because it
doesn't cross the blood brain barrier, is how that affects
the brain and whether our-- if we can independently activate
our adrenals, when a time when our brain thinks that we should
be fine and calm and asleep, how our brain detects that. Is it a feedback
through heart is racing? And then our brainstem
says, what's going on, my heart is racing,
and then wakes us up. And then our hearts were racing
together with our brain racing. We just don't know the answers
to these questions yet. There are some good
studies, old studies. But we need a lot more. ANDREW HUBERMAN: I will--
another nod to the fact that there's lots of great
work ongoing and still to do. I'd love for you to tell
us about some of the work that you're doing more
recently on the relationship between sleep and
opiate use, withdrawal relapse, and craving,
just addiction, generally. I get a lot of questions
about people trying to come off benzodiazepines
or people's challenges with benzodiazepine and
other types of addiction. What is the role of sleep
in addiction and recovery from addiction and
opiates in particular? GINA POE: Yeah. This is a very young area. And in fact, my laboratory
has just started. I have a graduate student
who's been in my lab for just one year. She's done amazing work already
but completely groundbreaking work. And what she has
discovered already-- we don't have the paper out
yet, but we're working on it-- is that when animals
withdraw from opiates-- and this has been
replicated in other ways with other types of things-- our sleep is disturbed. Our sleep is terribly disturbed. And the amount of
sleep disturbance predicts relapse behaviors. And you might think,
well, of course, you're going to relapse
if you can't sleep because opiates calm you down. Well, then one of the reasons
why opiates calm you down is because the locus coeruleus,
again, the blue spot, is covered with
opiate receptors that are normally really responsive
to our endogenous opiates. And so what happens
when we are pleased, for example, or
laughing or whatever, endogenous dodges
opiates activate those receptors in the locus
coeruleus and calm it down. It actually suppresses
locus coeruleus activity. It makes us happy and relaxed. One of the things, reasons
why opiates are so addictive is because it also calms us
down and makes us relaxed. But the problem with
exogenous opiates is that they really strongly
bind these receptors on our locus coeruleus. And if you take exogenous
opiates again and again like you're recovering
from surgery, for example, and take these
pain medications is that our locus
coeruleus struggles to do what it's supposed to
do which is keep us awake, and learning, and
concentrating on things. So it will down regulate. It will internalize
these receptors that are normally only
occupied by endogenous opiates. And it will do
this-- it will change our genes that are associated
with producing these receptors. So you actually have very
many fewer receptors. So the locus coeruleus, at
least, during wakefulness can fire and to help us
to do these things learn about our environment. And so if you long term
reduce the number of receptors out there, then when you
withdraw the exogenous opiate, there is not enough
of your endogenous opiates to be able to occupy
those few receptors that are there. And our locus has nothing
to calm it down anymore, no pacifier. And it just fires,
and fires, and fires. And that physic and
tonic high activity stresses us out,
because it's normally associated with stress. And so any exogenous
stressor that adds to that and also activates
our locus coeruleus, there's nothing to
calm it down again. And so it just keeps firing. It disturbs our sleep. And that's why maybe
sleep disturbance is an indicator of
hyperactive locus coeruleus and such a good
predictor of relapse behaviors because nobody likes
to live in that high stress state. And they will do anything
to get back to normal. So the problem with
taking these drugs is that it leaves you excited-- I'm sorry, excited,
relaxed and happy. But then when you
come off of it, you're worse than when
you were at baseline. You take it again. It only brings you up
this far, because you have fewer receptors. When you come off it, you're
down, even more depressed and anxious and-- depressed is a
word I use loosely, and that's not what I-- ANDREW HUBERMAN: Certainly,
central nervous system depression, sleepier, less
motivated, lower mood. GINA POE: Yeah. Our locus coeruleus
is actually-- it's a anxiety kind of
depression actually, the anxiety related depression. So yeah. So we don't know yet what-- and there's some good
research going on right now-- what could restore our own
endogenous receptors so that our endogenous opiates
can properly calm our locus coeruleus once that they
have been tamped down by exogenous opiates. But that would be really one way
that you can access the sleep disturbance. So we talked about sleep
and the importance of sleep in terms of learning and
memory, the importance of the structure of the
90-minute cycle for all of that. So you can imagine if your
sleep is disturbed by too much locus coeruleus activity. The structure and the function
of those sleep spindles and that theta during REM sleep
and the lack of norepinephrine, all of those structures, all
those functions for learning something new, like a new
behavior that doesn't involve the drugs becomes compromised. And so that's something that
Tania Lugo, in collaboration with Pamela Kennedy
at UCLA, that we're looking at how is learning and
memory affected by the sleep disturbance. If there's a way we can-- in animals that are
coming off of opiates. Can we restore their
sleep to normal so that then they
are less likely to do relapse kinds of behaviors. ANDREW HUBERMAN: Fascinating. And I will certainly have to
have you back on to tell us the results of those studies. Meanwhile, I think
for anyone who's trying to come off
opiates, exogenous opiates and restore these
systems, what I'm hearing is that it's going to take
some time but that any and all things that people
can do to buffer their healthy normal sleep
architecture like morning and daytime sunlight, limiting
bright light exposure, lowering the temperature at
night, a number of things that we've talked
about in this podcast-- GINA POE: Breathing
exercises, meditation, whatever it is that helps you
calm yourself before sleep, yeah. ANDREW HUBERMAN: Right. Would facilitate not just sleep
but perhaps even accelerate the recovery and
shorten this period of withdrawal, which
from the questions I get and from what I hear can
be absolutely brutal. GINA POE: Yeah. Oh, I can imagine. I had to take opiates for-- I only took it for three
days after giving birth to my first son, I think,
second son, one of them. And just-- I just said after
three days, this is enough. I'm just going to try Tylenol. And so I weaned
myself-- not weaned, I just did a sudden
sharp cut off. And even though I felt-- I didn't get the high
of opiates when I was taking the Tylenol codeine. When I went off it, boy,
it was like PMS times 100. I was so anxious and
upset at little things. And thankfully, it only
lasted a few hours. But if I had taken it
for a week or two weeks, who knows if my endogenous
opiate receptors would have been permanently
downregulated and I would have
been an addict-- or an addict-- I would
have been addicted. I shouldn't say an addict. There's negative connotations. It's just a very
physiological state. So no judgments at all
associated with it. So yeah, They're powerful,
powerful painkillers but can also alter your
entire brain and rewire it. ANDREW HUBERMAN: Well,
all the more reason why I and many others
are grateful that you're doing this work
to figure out ways that people can recover more
quickly and more thoroughly. I must say you've taught
us a tremendous amount in a relatively
short amount of time about the architecture of
sleep, the different phases, the relationship between
sleep and dreaming and this incredible
structure, locus coeruleus. And I'm so happy we
also got into the pons. That just delights me,
because we rarely talk about the pons on this podcast. It's such an
interesting structure. Sex differences that are
important in creativity and problem solving and trauma
sleep spindles, just such a wealth of information. And much of it that's
actionable for people. So first of all, I
want to say thank you for taking the time
to sit down and have this conversation that
so many people are sure to benefit from. I also want to thank you
for doing the work you do. Even though I'm a
fellow neurobiologist, I think that it's not often that
we take a step back and realize that it's really
the work of hard-- thinking hard, strongly
motivated PIs-- it stands for
principal investigator by the way, PIs like
yourself, graduate students, and post-docs that really
drive the discovery forward and that lead to these
new therapeutics. Physicians are wonderful. Clinicians are
absolutely wonderful. But clinicians don't
develop new treatments. They only implement the ones
that researchers discover. So thank you for
being a brain explorer with a focus on growing
the good in the world. I know I speak for everybody
when I say thank you so much. GINA POE: Thank you
so much, Andrew. Thank you for being an
amazing interviewer. You brought a lot out of
me in a coherent fashion that normally I can't do
when I'm speaking in public. ANDREW HUBERMAN: I
don't know about that. I've heard your lectures,
and they're superb. We'll direct people to
some of the other ones. GINA POE: Well, thank you. And I also want to put a
plug-in for graduate students in general and the
key and amazing role that they play in research. I'm a PI, as you said. I used to be a graduate student
and a post-doc trainee myself, doing all of this on the ground
hands on experimentation. It's so hard to do. It's so hard to do, right? It's so hard to think
through all of that. Now, I'm a PI, I get
to be an idea person and just say, hey,
why don't you do this and hey, what do you
think about that. And they, of course,
intellectually contributes so much to
these planned experiments. But they also do the
really hard work. And so I just want to say
thank you graduate students. Thank you to my
graduate students and all graduate
students out there. Thank you post-docs. ANDREW HUBERMAN: --underpaid. And listen, and to the major
institutions, Stanford UCLA and all other major
institutions, pay them more, please. GINA POE: Yes. ANDREW HUBERMAN: We need them. And they need to have
a standard of living. I'm not afraid to say that
despite my primary employer. Pay them more. They need it. They deserve it. GINA POE: They deserve
it, absolutely. ANDREW HUBERMAN: Great. Well, we will absolutely
have you back again if you'll be willing. And meanwhile, we
will direct people to where they can
learn more about you and your exciting work. And once again, thanks so much. GINA POE: Thank you so much. ANDREW HUBERMAN: Thank
you for joining me today for my discussion about sleep,
mental health, physical health, and performance
with Dr. Gina Poe. I hope you found it to be as
informative and as actionable as I did. In fact, I'm already
implementing the regularity of bedtime plus or
minus half an hour in order to get that
growth hormone release. And I can already see
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interest in science. [MUSIC PLAYING]
What do you guys do after 7pm or 8pm that doesn’t involve screen time and other light? I’ve tried audiobooks but often get very bored and have to slog through. An hour of that before bed can feel very long
“Sleep inertia” is mentioned, but what about “Wake inertia” aka when I push through that exhausted feeling after work around 6-9pm so I don’t ruin my sleep, only to be wide awake at midnight.
Transcript of this episode with timestamps and speakers: https://podscript.ai/podcasts/huberman-lab-podcast/dr-gina-poe-use-sleep-to-enhance-learning-memory-emotional-state/