Use Sleep to Enhance Learning, Memory & Emotional State | Dr. Gina Poe

Andrew Huberman 0:00 (music plays) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology 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,

Andrew Huberman 2:52 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, magnesium, and potassium, the so-called electrolytes, and no sugar. Now, the electrolytes are critical to the function of every cell in your body, in particular, the neurons, the nerve cells. As I've talked about before on this podcast, neurons, nerve cells require adequate sodium and potassium as well as magnesium in order to fire action potentials, which are the electrical signals that allow neurons to do everything from generate focus and attention, allow you to learn, and generate neuromuscular connection and allow you to exercise or train or do any kind of skilled activity with a high degree of output. I take LMNT about two or three times per day, typically once in the morning and again after or during my bout of exercise each day, and sometimes an additional one if I've sat in a hot sauna and sweat a lot or if the weather is very hot. If you'd like to try LMNT, you can go to Drink LMNT, that's L-M-N-T.com/huberman to claim a free LMNT sample pack with your purchase. Again, that's Drink LMNT, L-M-N-T.com/huberman to claim a free sample pack. Today's episode is also brought to us by Helix Sleep. Helix Sleep makes mattresses and pillows that are of the absolute highest quality. Now, sleep is the foundation of mental health, physical health, and performance. When we are sleeping well, all of those things excel. And when we are not sleeping well, all of those things suffer. Now, the surface that you sleep on, that is, the mattress that you sleep on, is critical. And Helix understands that everybody has slightly different sleep needs. So if you were to go to the Helix site, which I invite you to do, and take their brief two-minute quiz, it will match your body type and sleep preferences to the perfect mattress for you. It will ask you questions, for instance, do you sleep on your back or your side or your stomach? Do you tend to run hot or cold during the night? Or maybe you don't know the answers to those questions. I went and took the sleep quiz at Helix and it matched me to the so-called Dusk mattress, D-U-S-K. I started sleeping on a Dusk mattress over a year ago and it's the best sleep that I've ever had. It's completely transformed the depth and duration and quality of my sleep in ways that make me feel far better during the daytime. If you're interested in upgrading your mattress, you can go to helixsleep.com/huberman, take their two-minute sleep quiz, and they'll match you to a customized mattress and you'll get up to $350 off any mattress order and two free pillows. Again, if interested, go to helixsleep.com/huberman for up to $350 off and two free pillows. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity.Now, again, sleep is the foundation of mental health, physical health, and performance, but what many people don't realize is that in order to fall and stay asleep, your core body temperature has to drop by about one to three degrees. Conversely, in order to wake up each morning and feel refreshed, your body temperature actually has to increase by one to three degrees. Therefore, controlling the temperature of your sleeping environment is absolutely key. With Eight Sleep, that's very easy to do. Depending on whether or not you typically run too cold or too hot during the night, you can program your Eight Sleep mattress cover so that it's the optimal temperature, not just for you, but for each phase, the early, middle, and late phase of your sleep and for waking up in the morning. In fact, you can even control the temperature of your Eight Sleep mattress cover differentially across the mattress if you're sleeping alongside somebody else. If you'd like to try Eight Sleep, you can go to EightSleep.com/Huberman and check out their Pod Pro Cover and save $150 at checkout. Eight Sleep currently ships in the USA, Canada, UK, and select countries in the EU and Australia. Again, that's EightSleep.com/Huberman to save $150 at checkout. The Huberman Lab Podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to Live Momentous, spelled O-U-S, LiveMomentous.com/Huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's LiveMomentous.com/Huberman. And now for my discussion with Dr.

Andrew Huberman 6:58 Gina Po. Dr. Gina Po, welcome.

Gina Poe 7:00 Thank you.

Andrew Huberman 7:01 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-

Gina Poe 7:16 Mm-hmm.

Andrew Huberman 7:17 ... and a number of other important topics. So-

Gina Poe 7:20 Mm-hmm.

Andrew Huberman 7:20 ... 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.

Gina Poe 7:29 (laughs)

Andrew Huberman 7:29 And if you would, could you describe the various phases of sleep that exist, what distinguished them, and perhaps frame this within the context of what would a perfect night sleep look like?

Gina Poe 7:41 Okay.

Andrew Huberman 7:42 How long would it last, more or less?

Gina Poe 7:44 Mm-hmm.

Andrew Huberman 7:44 And what would the biology look like? What, w- what is a perfect night's sleep?

Gina Poe 7:49 Oh, 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. Um, our brain chemistry is completely different, and in the different stages of sleep, which there are, there's 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. Um, 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're first falling asleep. It's dozing, there's kind of an interesting rhythm that goes on in the brain that'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 then, a- 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. Um, one of the things that those big slow waves do is cleans our brain and does other really important things to restore us, um, 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, um, 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, 10:00, 10:30, 11:00, um, our first REM sleep period comes about 105 minutes after we fall asleep and, um, lasts about 20 minutes. Actually, it comes about 95 minutes and lasts 10 or 15 minutes, and then, uh, 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, um, 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 is because, 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-

Andrew Huberman 10:23 Mm-hmm.

Gina Poe 10:23 ... and they would round off to, on average, eight hours and 15 minutes a night and then they spend the rest of the time twiddling their thumbs, humming tunes, you know-

Andrew Huberman 10:30 Interesting.

Gina Poe 10:31 ... daydreaming.

Andrew Huberman 10:32 I want to get back to the contour of a perfect night's sleep-

Gina Poe 10:34 Mm-hmm.

Andrew Huberman 10:34 ... 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-

Gina Poe 10:40 Mm-hmm.

Andrew Huberman 10:40 ... and whether or not sleeping too log, long, excuse me, can make us groggy the next day.

Gina Poe 10:45 Right.

Andrew Huberman 10:45 Um, is there anything to that?

Gina Poe 10:47 Okay.

Andrew Huberman 10:47 Um, and how does one determine how long they should sleep-

Gina Poe 10:51 Right.

Andrew Huberman 10:51 ... on average?

Gina Poe 10:52 On average, yeah. Well, that's interesting because different people need, seem to need different amounts of sleep, but we don't really even know exactly what sleep is for. So what they need is, you know, kind of, it's, ye- you know, mercury- murky. Um, so we do know a lot of things that sleep do, does now for us, but we don't know how long those things take. So, how long, uh, we need to sleep is also just a big question mark. But some people don't feel rested until they've slept nine hours and some people don't feel rested after three or four and a half. Um, but most people, if they consistently deprive themselves of sleep so that they're only sleeping four, 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 depr- 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 11:54 Can you overs-

Gina Poe 11:55 Can you oversleep? Right.

Andrew Huberman 11:56 Can you sleep to the point where it's too much, you know, that we, I-

Gina Poe 11:59 Yeah.

Andrew Huberman 11:59 Growing up, um, uh, when I was in high school, uh, my girlfriend's dad-

Gina Poe 12:03 Mm-hmm.

Andrew Huberman 12:03 ... had this belief that no one should sleep in past 6:00 AM. So he would, he'd wake all the, there were two children-

Gina Poe 12:10 (laughs)

Andrew Huberman 12:10 ... in that home. He would wake up the kids in that house. He had this thing against oversleeping-

Gina Poe 12:13 (laughs)

Andrew Huberman 12:13 ... regardless of when people went-

Gina Poe 12:15 Right.

Andrew Huberman 12:15 ... went to sleep. And I always thought that was, um, an interesting mentality.

Gina Poe 12:18 Yeah.

Andrew Huberman 12:19 Um, I don't-

Gina Poe 12:19 It's not terrible actually, because what that will do is it'll put you, make you sleepier the next night to get to bed on time. So-

Andrew Huberman 12:27 Mm-hmm.

Gina Poe 12:27 ... it'll build up your homeostatic need if you wake up too early. But, um, so I don't think you can oversleep, but people who sleep a lot, like people who sleep over nine hours-

Andrew Huberman 12:37 Mm-hmm.

Gina Poe 12:37 ... it's probably indicative of some other problem because, in fact, if you have, um, 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-

Andrew Huberman 12:59 Mm-hmm.

Gina Poe 12:59 ... maybe what else it might be. It could be cancer, it could be, um, sleep apnea, that just affects a lot of people. It could be that your sleep is super inefficient because you's 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 13:22 And that wouldn't be if somebody is sleeping 9 or 10 hours, you know, every once in a while. You mean if they're consistently-

Gina Poe 13:28 Yeah.

Andrew Huberman 13:28 ... sleeping for m- more than nine hours.

Gina Poe 13:30 If they feel like they need it in order to function cognitively the next day, it, it might be that your sleep is just not efficient. And you might want to look into why that, that's the case.

Andrew Huberman 13:40 Interesting.

Gina Poe 13:41 Yeah.

Andrew Huberman 13:41 Uh, forgive me for the anecdote, but I can't resist.

Gina Poe 13:43 (laughs)

Andrew Huberman 13:43 Years ago, I went to an acupuncturist and, um, he gave me these red pills-

Gina Poe 13:49 (laughs)

Andrew Huberman 13:49 ... um, of which I don't know what they contained.

Gina Poe 13:51 Uh-oh. (laughs)

Andrew Huberman 13:52 But I took them-

Gina Poe 13:53 (laughs)

Andrew Huberman 13:53 ... because he told me they would help with my sleep.

Gina Poe 13:55 Okay.

Andrew Huberman 13:55 And I would fall asleep about 30 minutes after taking them.

Gina Poe 13:58 Mm-hmm.

Andrew Huberman 13:58 And I would have incred- incredibly, excuse me, vivid dreams.

Gina Poe 14:02 Mm-hmm.

Andrew Huberman 14:03 And I'd wake up four or five hours after having gone to sleep, feeling completely rested. Something that I've never really experienced-

Gina Poe 14:10 Interesting.

Andrew Huberman 14:10 ... on a consistent basis.

Gina Poe 14:11 Hmm.

Andrew Huberman 14:12 I want to do mass spec on these pills.

Gina Poe 14:13 Yeah.

Andrew Huberman 14:14 I still have no idea what was in them-

Gina Poe 14:15 (laughs)

Andrew Huberman 14:15 ... whatsoever.

Gina Poe 14:16 I want to do mass spec on those pills too. (laughs)

Andrew Huberman 14:17 Yeah, exactly. Some people had thought, um, that perhaps they had GHB, gamma-hydroxybutyrate-

Gina Poe 14:21 Mm-mm.

Andrew Huberman 14:21 ... which is, by the way, an illegal drug. It can kill you. It's not a, not something you want to take.

Gina Poe 14:25 No, that's not good.

Andrew Huberman 14:26 Um, but anyway, if, if ever someone can figure out what the red pills were, I'll be very, um...

Gina Poe 14:31 (laughs) That's really great.

Andrew Huberman 14:31 And this is not a red pill of the, of the other sort red pill. This is just the red sleep pills. Um-

Gina Poe 14:36 Interesting. I mean, could have been even a placebo effect because placebo is extremely strong. So, um...

Andrew Huberman 14:42 Yeah, although, I, I don't know, there was really something to these red pills.

Gina Poe 14:45 Okay. (laughs) I

Narrator 14:45 would imagine.

Andrew Huberman 14:45 So, uh, shout out to the acupuncturist and, uh-

Gina Poe 14:48 (laughs)

Andrew Huberman 14:48 ... and the Eastern medicine.

Andrew Huberman 14:50 Um, but to return this i- to this idea of the architecture of a perfect night's sleep.

Gina Poe 14:56 Mm-hmm.

Andrew Huberman 14:56 So you said, um, we fall asleep, the first 90 minutes of sleep, REM sleep, rapid eye movement sleep will arrive at about 95 minutes in.

Gina Poe 15:05 Yeah.

Andrew Huberman 15:05 Does that mean that the rest of that 90 minutes is consumed with slow wave sleep?

Gina Poe 15:11 Yeah, non-REM sleep.

Andrew Huberman 15:12 Okay. And what about the sleep where we are lightly asleep-

Gina Poe 15:16 Mm-hmm.

Andrew Huberman 15:16 ... and we might have a dream that has us somehow thinking about movement or that we jolt ourselves awake?

Gina Poe 15:22 Yeah. Yeah.

Andrew Huberman 15:22 That often happens early in the night, right?

Gina Poe 15:24 Yeah. Yeah. That's the first stage, stage one and stage two of sleep, and stage two of sleep is really cool because that has something called sleep spindles and K-complexes. And what sleep spindles are, are, um, a little brr of activity that's 10 to 15 hertz in frequency. It's a conversation between the thalamus and the cortex. The ga- thalamus is the gateway to consciousness and the neocortex, you know, processes all our cognition. And, um, so it's, 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.

Andrew Huberman 16:11 Mm-hmm.

Gina Poe 16:12 And during, 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-

Andrew Huberman 16:19 Mm-hmm.

Gina Poe 16:19 ... 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, we'll feel like... It'll be, include some falling aspect that we'll wake up out of.

Andrew Huberman 16:37 That's really interesting to me.

Gina Poe 16:39 Mm-hmm.

Andrew Huberman 16:39 I've long felt that sensation of almost like dropping back into my head.

Gina Poe 16:44 Mm-hmm.

Andrew Huberman 16:45 Um, so much so that if I elevate my s- feet just slightly and I tilt my head back-

Gina Poe 16:49 Mm-hmm.

Andrew Huberman 16:49 ... just slightly-

Gina Poe 16:50 Mm-hmm.

Andrew Huberman 16:50 ... um, in order to go to sleep, I find that I fall asleep mus- much faster.

Gina Poe 16:53 Interesting.

Andrew Huberman 16:54 But it does feel as if I'm going to fall, like almost going to do a backward somersault.

Gina Poe 16:57 That's fascinating.

Andrew Huberman 16:57 I actually really like the, the sensation-

Gina Poe 16:59 (laughs)

Andrew Huberman 16:59 ... and usually because it precedes falling deeply asleep.

Gina Poe 17:01 Yeah, that's really interesting.

Andrew Huberman 17:03 Yeah.

Gina Poe 17:03 I'm, somebody has to do a study of elevated feet and... (laughs)

Andrew Huberman 17:07 Yeah, there, I think there's a little bit on, um, body position-

Gina Poe 17:10 Mm-hmm.

Andrew Huberman 17:10 ... and sleep and some of the washout that we'll talk about. So early in the night, um, you got these l- lighter stages of sleep, less rapid eye movement sleep. What can we say about the dreams that occur during the, say, first and second, um, you know, 90-minute cycles of sleep?

Gina Poe 17:26 Yeah.

Andrew Huberman 17:26 Are they quite different than the patterns of sleep, uh, and dreaming that occur later in the night or toward morning?

Gina Poe 17:32 Well, okay, that's an interesting question. There's a lot of facets to it. Um, there is some evidence that the first four hours of sleep are very important for memory processing. Um, and in fact, the-... if you've learned something new that day or have experienced a new, um, sensory motor experience, then your early sleep dreams will incorporate that experience much more than the later sleep dreams. Um, 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, um, nobody knows why but it does. There was a great study by Sidarto Ribeiro who studied the consolidation of memories from the cortex, 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 fir- first area that projects to it, and then the second area, and then the third area. And you can see the memory moving, um, through the, throughout the sleep-

Andrew Huberman 18:57 Cool.

Gina Poe 18:57 ... period. Yeah.

Andrew Huberman 18:58 Very cool.

Gina Poe 18:59 Yeah.

Andrew Huberman 18:59 So I have to read that study.

Andrew Huberman 19:01 So, um, there's a number of different hormones associated with the different stages of sleep. We know that melatonin is a hormone that-

Gina Poe 19:09 Of nighttime.

Andrew Huberman 19:10 ... of nighttime that makes us sleepy.

Gina Poe 19:12 Mm-hmm.

Andrew Huberman 19:12 Um, what about growth hormone release? When does that occur during sleep?

Gina Poe 19:15 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, um, is when you get a big bolus of growth hormone release and 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 prot- proteins. Um, 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, needs more synaptic space to encode it.

Andrew Huberman 20:15 How would somebody miss that first 90 minutes?

Gina Poe 20:18 Sleep-depriving themselves. Yeah, so you could-

Andrew Huberman 20:20 So let's say I normally go to sleep at, um, 10:00 PM.

Gina Poe 20:22 Mm-hmm.

Andrew Huberman 20:23 Um, and then from 10:00 to 11:30 would be this first phase of sleep and that's when the growth hor- big bolus-

Gina Poe 20:29 Yeah.

Andrew Huberman 20:30 ... of growth hormone would be released. Does that mean that if I go to sleep instead at 11:30 or midnight that I miss that first phase of sleep?

Gina Poe 20:37 Yeah.

Andrew Huberman 20:37 Why is it not the case that I get that first phase of sleep just simply starting later?

Gina Poe 20:41 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 those clocks are normally synchronized and the circadi- 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 me- melatonin also, so if you miss it, yeah, you might get some growth hormone release but it's occurring at a time when that, your clock is already moved to the next phase. And so it's, it's just a clock thing.

Andrew Huberman 21:18 Yeah. I don't think, um, we can overstate the importance of what you just described.

Gina Poe 21:22 Mm-mm.

Andrew Huberman 21:22 And to be honest, despite knowing a bit about the sleep research and circadian biology-

Gina Poe 21:26 Mm.

Andrew Huberman 21:27 ... 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 bout later and expect to capture that first phase of sleep.

Gina Poe 21:41 Yeah.

Andrew Huberman 21:42 That's incredible.

Gina Poe 21:43 Mm-hmm.

Andrew Huberman 21:43 And I think important.

Gina Poe 21:44 Mm-hmm.

Andrew Huberman 21:45 And, um, as many listeners are probably realizing, also highly actionable. So what this means is that we should have fairly consistent bedtimes-

Gina Poe 21:52 Yes.

Andrew Huberman 21:52 ... in addition to fairly consistent wake times.

Gina Poe 21:54 Yes.

Andrew Huberman 21:54 Is that right?

Gina Poe 21:55 Exactly. And in fact one of the best markers of good neurological health when we get older is consistent bedtimes.

Andrew Huberman 22:04 Wow.

Andrew Huberman 22:05 Okay. Um, I don't want to backtrack but I did write down something that I think is, um, important for me to resolve, um, or for you to resolve.

Gina Poe 22:14 Mm-hmm.

Andrew Huberman 22:14 So I'm going to ask this. Um, people that sleep nine hours or more, perhaps that reflecting an issue, some underlying issue perhaps.

Gina Poe 22:22 Mm-hmm.

Andrew Huberman 22:22 Is being a teenager or an adolescent and undergoing a stage of, of, of development where there's a lot of bodily and brain growth an exception to that because-

Gina Poe 22:31 Yes.

Andrew Huberman 22:31 ... I don't recall sleeping a ton when I was a teenager. I had a ton of energy.

Gina Poe 22:36 Yeah.

Andrew Huberman 22:36 But I know a few teenagers, um, and they sleep a lot.

Gina Poe 22:40 Yeah. Yeah.

Andrew Huberman 22:41 Like they'll just sleep and sleep and sleep and sleep.

Gina Poe 22:42 Yeah.

Andrew Huberman 22:43 Should we let them sleep and sleep and sleep?

Gina Poe 22:44 Yes.

Andrew Huberman 22:44 Okay.

Gina Poe 22:45 Let them sleep. (laughs)

Andrew Huberman 22:45 Okay. So that's the one exception. What about if-

Gina Poe 22:47 Just like babies.

Andrew Huberman 22:48 Okay.

Gina Poe 22:48 Eh, when, when you're developing something in your brain or the rest of your body, you really need sleep to help organize that. I mean, sleep is doing really hard work in organizing our brains and, and making it develop right. And if we deprive ourselves of sleep, we will actually also just ha- like, 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 23:16 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-

Gina Poe 23:25 Mm-hmm.

Andrew Huberman 23:25 ... are there things that I perhaps do in the preceding hours or 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 23:37 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, um, to our cortex. It's a unique time when our hippocampus, the sort of like the RAM of our brains, um, writes it to a hard disk and, uh, which is the cortex. And they're, 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 ch- is also a part of the consolidation process and, um, schema changing process and alcohol in there, you know, 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, uh, badly.

Andrew Huberman 24:24 So probably fair to say no ingestion of alcohol within the four to six hours preceding sleep?

Gina Poe 24:31 Yeah. (laughs)

Andrew Huberman 24:32 Given the half-life?

Gina Poe 24:33 (laughs) Given the half-life.

Andrew Huberman 24:33 Or at all, or at all would be better-

Gina Poe 24:35 Yeah.

Andrew Huberman 24:35 ... but I know some people r- refuse to go that way.

Gina Poe 24:37 Maybe a little bit is okay. I don't know what the dose response is, but, um, there are studies out there you can look at.

Andrew Huberman 24:44 Great.

Gina Poe 24:45 Yeah.

Andrew Huberman 24:46 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.

Gina Poe 24:54 Yeah.

Andrew Huberman 24:54 What about the

Andrew Huberman 24:55 second and third 90 minute blocks of sleep? Is there anything that makes those, um, unique? What, what is their signature, uh, besides the fact that they come second and third in the night?

Gina Poe 25:04 Yeah. There's more and more REM sleep the later in the night we get. Um, there's also a change in hormones, you know, the growth hormone and, um, 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.

Andrew Huberman 25:32 Hm.

Gina Poe 25:32 That's when our dreams can incorporate and put together old and new things together into a new way and, um, and our schema are built during that time. So, um, yeah, we can change our minds best during those phases of sleep.

Andrew Huberman 25:48 Could you elaborate a little bit more on schema?

Gina Poe 25:50 Yeah.

Andrew Huberman 25:51 Uh, no one... I don't think anyone on this podcast has ever discussed schema.

Gina Poe 25:54 No.

Andrew Huberman 25:54 I'm a little bit familiar with schema from my, um, courses on psychology, but it's been a while, so maybe if you could just refresh mine and everyone, everyone else's memory.

Gina Poe 26:01 Well, it's, it's still a, a concept.

Andrew Huberman 26:03 Sure.

Gina Poe 26:04 Schema is this concept. (laughs)

Andrew Huberman 26:05 How do you define schema?

Gina Poe 26:06 Right. (laughs) I think of schema as, um, like we have a schema of Christmas, right? We ha- we, we have all kinds of ideas that we sew together and call 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 that, 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 y- ourselves a list of words and, um, and none of them contain the word Christmas and then ask people later, um, you know, give them another list of words and include the w- 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 is what I-

Andrew Huberman 27:04 When I think about it sort of like on the desktop of my computer, um, would scare some people, but it's just a ton of folders.

Gina Poe 27:10 Yeah. (laughs)

Andrew Huberman 27:10 But each of the folder names mean something-

Gina Poe 27:12 Yeah.

Andrew Huberman 27:12 ... very clear and specific to me.

Gina Poe 27:14 Right.

Andrew Huberman 27:14 And inside of those folders are collections of things that-

Gina Poe 27:17 That's right.

Andrew Huberman 27:17 ... make sense in terms of how they're batched.

Gina Poe 27:19 That's right.

Andrew Huberman 27:19 Is that kind of one way to think about it?

Gina Poe 27:20 Exactly. No, that's a great way to think of it. And, 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 com- opening folders and comparing documents, seeing if there, is there anything the same. These two documents look very much the same, but there's a little bit of difference and it can, it can link those conceptually. So that, 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-

Andrew Huberman 27:52 Mm-hmm.

Gina Poe 27:52 ... you know, makes your schema interesting and different. Yeah.

Andrew Huberman 27:56 Very interesting.

Gina Poe 27:57 Mm-hmm.

Andrew Huberman 27:57 Um, many people, including myself, tend to wake up maybe once during the middle of the night to use the restroom.

Gina Poe 28:03 Mm-hmm.

Andrew Huberman 28:03 I've tried to drink less fluid before going to sleep. I've, I've heard also that, um, the impulse to urinate, forgive the topic-

Gina Poe 28:12 Mm-hmm.

Andrew Huberman 28:12 ... but a lot of people deal with this, so the impulse to urinate is also dictated by how quickly you drink fluid.

Gina Poe 28:17 Mm-hmm.

Andrew Huberman 28:17 Not just the total volume.

Gina Poe 28:18 Mm-hmm.

Andrew Huberman 28:18 So I've switched to, um, sipping fluids more slowly for my last beverage of the day-

Gina Poe 28:22 Mm-hmm. Yeah.

Andrew Huberman 28:22 ... 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-

Gina Poe 28:26 Mm-hmm.

Andrew Huberman 28:26 ... oftentimes to use the restroom-

Gina Poe 28:28 Mm-hmm.

Andrew Huberman 28:28 ... but oftentimes just around 3:00 AM-

Gina Poe 28:30 Mm-hmm.

Andrew Huberman 28:31 ... and might be up for a few minutes, hopefully not on their phone or viewing any bright light-

Gina Poe 28:34 Mm-hmm.

Andrew Huberman 28:34 ... which can cause more wakefulness, but then go back to sleep.

Gina Poe 28:38 Yeah.

Andrew Huberman 28:38 Is there any known detriment to this middle of the night waking-

Gina Poe 28:42 No.

Andrew Huberman 28:42 ... or should we consider it a normal feature for some people's sleep architecture?

Gina Poe 28:47 Yeah, I think we shouldn't worry about it actually. I think, you know, 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. Um, 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, um, you know, 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, um, or going to bed a little earlier.

Andrew Huberman 29:31 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-

Gina Poe 29:38 Mm-hmm.

Andrew Huberman 29:38 ... and you have to get it by going to sleep-

Gina Poe 29:40 Yeah.

Andrew Huberman 29:40 ... essentially-... the same time each night-

Gina Poe 29:42 Right.

Andrew Huberman 29:42 ... maybe plus or minus 15 minutes or so.

Gina Poe 29:44 Yeah. Yeah.

Andrew Huberman 29:45 Um, but then if I wake up in the middle of the night and go back to sleep, I can, not 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 29:54 Yeah. Yeah. Yeah.

Andrew Huberman 29:55 Okay.

Gina Poe 29:55 Yeah. And, 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 30:12 Well, I suppose I am the experiment in that case-

Gina Poe 30:14 (laughs) .

Andrew Huberman 30:14 ... because I do tend to wake up once per night, and I've, I've sort of come to, um, recognize it as part of my normal sleep architecture.

Gina Poe 30:20 Mm-hmm.

Andrew Huberman 30:20 I don't obsess over it.

Gina Poe 30:21 Right.

Andrew Huberman 30:22 I do notice that when I go back to sleep, and especially toward morning-

Gina Poe 30:25 Mm-hmm.

Andrew Huberman 30:26 ... that my sleep is incredibly deep.

Gina Poe 30:28 Mm-hmm.

Andrew Huberman 30:28 My dreams are incredibly vivid.

Gina Poe 30:30 Oh, that's great.

Andrew Huberman 30:30 I don't always remember them-

Gina Poe 30:32 Yeah.

Andrew Huberman 30:32 ... but wha- what

Andrew Huberman 30:33 is unique perhaps about the architecture of dreams and sleep in the, let's say, the last third of the night or the-

Gina Poe 30:40 Yeah.

Andrew Huberman 30:40 ... or the second half of the night?

Gina Poe 30:41 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 waves is considered deep. It is deep, but actually-

Andrew Huberman 30:53 Yeah. They call slow wave sleep deep sleep-

Gina Poe 30:55 Yeah.

Andrew Huberman 30:55 ... and REM sleep rapid eye movement. But now you're telling me that REM sleep is actually the deeper sleep?

Gina Poe 30:59 The deepest.

Andrew Huberman 30:59 Okay. There needs to be a new nomenclature-

Gina Poe 31:01 Yeah. (laughs)

Andrew Huberman 31:01 ... of sleep researchers.

Gina Poe 31:02 I know. You really shouldn't call it-

Andrew Huberman 31:03 Yeah.

Gina Poe 31:03 ... deep or not deep.

Andrew Huberman 31:03 No. No. Please.

Gina Poe 31:04 The reason why you call slow wave sleep deep sleep is because it's difficult to arouse people out of that state. Um, and when you do arouse them out of that state, they're more s- 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 kind of almost like wakefulness, it's, it was so vivid. But in fact, if you give someone a non-threatening kind of stimulation, like somebody dropping keys or, um, 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, y- rapid eye movements more dense, and often people will incorporate that sound into their dreams. So-

Andrew Huberman 31:54 Hmm. So the body and brain are somehow conscious of the, um, of the sound, and I've heard also smells-

Gina Poe 32:01 Mm-hmm.

Andrew Huberman 32:01 ... can even make it into our, our dreams-

Gina Poe 32:03 Mm-hmm.

Andrew Huberman 32:03 ... in, in REM sleep, but that we, it doesn't arouse us for sleep.

Gina Poe 32:07 It doesn't arouse us as often. Yeah.

Andrew Huberman 32:09 Interesting.

Gina Poe 32:09 And maybe one of the reasons why REM sleep is deeper is, 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 they... It's really hard to wake them up out of that deep slow wave sleep. And in fact, um, 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 (imitates fire alarm) whatever, they don't associate with, it says their name or something else that may be less loud but more salient to them and will wake them up.

Andrew Huberman 33:02 I don't know, having carried sleeping children in from the car-

Gina Poe 33:05 Yeah.

Andrew Huberman 33:05 ... I don't know that I want children to start waking up from sleep 'cause-

Gina Poe 33:08 Yeah. I know.

Andrew Huberman 33:08 ... that's one of the best things when you get-

Gina Poe 33:09 Isn't it?

Andrew Huberman 33:09 ... home and the kids are asleep in the back seat.

Gina Poe 33:11 (laughs) Yeah.

Andrew Huberman 33:11 You can literally throw them over your shoulder.

Gina Poe 33:13 Yeah. Yes.

Andrew Huberman 33:13 Gently of course.

Gina Poe 33:14 Yes.

Andrew Huberman 33:15 And put them to sleep and, and i- they are completely out.

Gina Poe 33:18 They're safe. Yeah.

Andrew Huberman 33:18 They're completely out.

Gina Poe 33:18 It's wonderful.

Andrew Huberman 33:19 It is wonderful.

Gina Poe 33:20 (laughs)

Andrew Huberman 33:20 One o- one of nature's gifts.

Andrew Huberman 33:22 I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3 K2.

Andrew Huberman 34:37 So this, um, enhanced volume or, or proportion of, of rapid eye movement sleep in the second half of the night, uh, relates to more elaborate dreams. Uh, we are paralyzed during-

Gina Poe 34:48 Mm-hmm.

Andrew Huberman 34:49 ... REM sleep, correct?

Gina Poe 34:49 Yes.

Andrew Huberman 34:50 Yeah.

Gina Poe 34:50 Normally paralyzed and that's really good because that's the time when we're actively dreaming storyline dreams and we could, um, hurt ourselves. We're actually really cut off from the outside world in terms of, you know, um, responding to, say, this table or window or door, and so different from s- sleepwalking, which is out of slow wave sleep, uh, out of slow wave sleep, that sleepwalking is a mixture between sleep and wakefulness, so you actually will respond to the door. You can cook a full meal, um, 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, voluntary control over it. You have no conscious control over it, but you can actually safely navigate, um, some situations in sleepwalking, um, and actually have a conversation, although it may not make much sense when you're sleep talking. In REM sleep, you're not a-... processing the outside world. And instead, um, when you're acting out your dreams, you could be doing things like walking through a plate glass window or falling off of, you know, down the stairs, um, 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 36:09 What about sleep talking or talking in sleep?

Gina Poe 36:11 Mm-hmm.

Andrew Huberman 36:12 Um, I don't know how many relationships have, um, been saved by sleep talking, but I'm guessing a few have, uh, been destroyed.

Gina Poe 36:18 (laughs) Yeah.

Andrew Huberman 36:18 And I'm guessing that, um, talking in sleep could have meaning or perhaps has no meaning, just as dreams-

Gina Poe 36:24 Yeah.

Andrew Huberman 36:25 ... could have meaning or no meaning-

Gina Poe 36:26 Yeah.

Andrew Huberman 36:26 ... as we recall them. Yeah.

Gina Poe 36:28 Yeah. Do not take sleep talking seriously. Um, 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. Um-

Andrew Huberman 36:37 You just saved a number of relationships.

Gina Poe 36:39 I hope so. (laughs)

Andrew Huberman 36:40 (laughs) Um, I'm not directing this at anyone in particular-

Gina Poe 36:42 (laughs)

Andrew Huberman 36:43 ... but I, I guarantee you just did.

Gina Poe 36:44 Yeah.

Andrew Huberman 36:45 Um, noted.

Gina Poe 36:46 (laughs)

Andrew Huberman 36:47 Um, so as people start to approach morning or the time when they normally would wake up-

Gina Poe 36:52 Mm-hmm.

Andrew Huberman 36:54 ... I've heard that it's important to, if possible, complete one of these 90-minute cycles prior to waking up.

Gina Poe 37:01 Hmm.

Andrew Huberman 37:01 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, um, rather groggy patterns of waking.

Gina Poe 37:14 Mm-hmm.

Andrew Huberman 37:14 Um, so I'll just ask you directly, do you use a, uh, an alarm clock?

Gina Poe 37:17 I do not. Um, thankfully, I'm in a line of work that doesn't require me normally to do anything at any particular time.

Andrew Huberman 37:24 That's great.

Gina Poe 37:24 I do it when I do it. Um-

Andrew Huberman 37:25 Great.

Gina Poe 37:26 ... unless I have to catch a plane, and then I always set my alarm just in case. (laughs)

Andrew Huberman 37:29 Well, as a fellow academic, I can tell you there are plenty of punishing features about being an academic scientist that-

Gina Poe 37:34 (laughs)

Andrew Huberman 37:34 ... um, that offset the fact that, uh, you don't have to use an alarm clock, but it is nice that you can often set your own schedule.

Gina Poe 37:40 Yeah. Yeah.

Andrew Huberman 37:40 So would you recommend that, if possible, that people not use an alarm clock?

Gina Poe 37:44 Yeah, absolutely. If you can just listen to your body and wake up when you need to wake up, that would be great. Um, but, um, one of the reasons why we have such grogginess is called sleep inertia. When we wake up out of the wrong state, which is, um, deep slow wave sleep, is because I liken it to, uh, like a washing machine cycle. This 90-minute cycle is like a washing machine cycle. And, and, um, the first part is to add water, right? And, um, 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, that's... Put it in the dryer too-

Andrew Huberman 38:28 Mm-hmm.

Gina Poe 38:28 ... (laughs) um, before you want to wear them. Um, so, yeah, you can function. It just takes a little while for those clothes, (laughs) that brain to dry out, so you can actually function well. Um, but it's better to wait through the whole cycle is complete. And so that's why you want to set that 90, 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-

Andrew Huberman 38:59 Mm-hmm.

Gina Poe 38:59 ... but then the second ones and third ones, they get sort of shorter and shorter as the night goes on. And in the last few cycles, you're just doing the N2 REM sleep cycle, which takes less time. And if you wake up out of REM sleep, there's usually no problem cognitively.

Andrew Huberman 39:14 Okay.

Gina Poe 39:14 You're, you're good to go.

Andrew Huberman 39:16 Are you a fan of, of sleep trackers?

Gina Poe 39:20 Uh, sure. Yeah.

Andrew Huberman 39:21 Yeah. Do you use one?

Gina Poe 39:22 I have one on.

Andrew Huberman 39:23 Mm-hmm.

Gina Poe 39:23 I don't take... I don't, I don't, um, live my life by them because they are... The best ones right now are about 70% effective at-

Andrew Huberman 39:34 Mm-hmm.

Gina Poe 39:34 ... staging your sleep. So 70%, it's okay.

Andrew Huberman 39:37 Yeah.

Gina Poe 39:37 It's, it's okay, but, um, take it with a grain of salt is what I'm saying.

Andrew Huberman 39:41 Yeah, I've tried various ones and I compare the mattress-based one to a-

Gina Poe 39:44 Mm-hmm.

Andrew Huberman 39:45 ... I actually wear it on my ankle instead-

Gina Poe 39:46 Mm-hmm.

Andrew Huberman 39:46 ... of my wrist, but-

Gina Poe 39:47 Mm-hmm.

Andrew Huberman 39:47 ... um, and I do find it informative, but a, um, a colleague of mine at Stanford, Alia Crum-

Gina Poe 39:52 Mm-hmm.

Andrew Huberman 39:52 ... who works on mindset and belief effects-

Gina Poe 39:54 Mm-hmm.

Andrew Huberman 39:55 ... talked to me about a study they did where people often will bias their sense of daytime wakefulness based on their sleep score-

Gina Poe 40:02 Oh, gosh.

Andrew Huberman 40:02 ... more than their subjective-

Gina Poe 40:04 Yeah.

Andrew Huberman 40:04 ... score.

Gina Poe 40:05 Yeah.

Andrew Huberman 40:05 Um, in other words, if they were told they got a poor night's sleep, even if they got a great night's sleep-

Gina Poe 40:09 Yeah.

Andrew Huberman 40:09 ... and the... and, and this was of course measured in the sleep lab-

Gina Poe 40:11 Yeah.

Andrew Huberman 40:11 ... so they, they're able to compare-

Gina Poe 40:12 Yeah.

Andrew Huberman 40:12 ... people report feeling more groggy.

Gina Poe 40:15 Yeah.

Andrew Huberman 40:15 And the opposite is also true-

Gina Poe 40:16 Yeah.

Andrew Huberman 40:16 ... that if it says 100% or 90% on your sleep score-

Gina Poe 40:19 Mm-hmm.

Andrew Huberman 40:19 ... then people go, "Oh, I feel great."

Gina Poe 40:20 Yeah.

Andrew Huberman 40:20 Even though they might not have slept well.

Gina Poe 40:21 Yeah.

Andrew Huberman 40:22 So this speaks to the, I don't want to say, placebo effect, but the sort of belief effects-

Gina Poe 40:25 Yeah.

Andrew Huberman 40:25 ... that are woven in with a score.

Gina Poe 40:26 Yes. That's right. Mm-hmm.

Andrew Huberman 40:28 Um, so it seems to me that combining subjective and objective data-

Gina Poe 40:31 Yeah.

Andrew Huberman 40:31 ... is probably best.

Gina Poe 40:32 Yeah. And I do believe that you should trust your own physiology and the way that your body is telling you to feel. Um, 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've, I didn't sleep very well at all." And that's because probably we, we just came out with a paper that shows that subcortical structures can be in a completely different sleep state than cortical structures as which is what we measure in the sleep lab, um, what the cortex is doing.

Andrew Huberman 41:07 Interesting.

Gina Poe 41:07 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," um, was because they're, they're monitoring their subcortical, um, hypothalamus, hippocampus, um, thalamus, other, other structures that the sleep lab just can't access unless you have depth electrodes, which nobody really wants.

Andrew Huberman 41:30 Right, 'cause that requires holes in the skull-

Gina Poe 41:33 Holes in the skull.

Andrew Huberman 41:33 ... and wires.

Gina Poe 41:34 Yeah. (laughs)

Andrew Huberman 41:34 Wow. So does that mean that the last 50 plus years of sleep science-

Gina Poe 41:38 (laughs)

Andrew Huberman 41:39 ... um, it's potentially flawed in some way because they're only recording from... Um, I guess this-

Gina Poe 41:44 Mm-hmm.

Andrew Huberman 41:44 ... would be, the analogy would be, it's like recording from the surface of the ocean-

Gina Poe 41:47 Yeah.

Andrew Huberman 41:48 ... as opposed to the depth of the ocean.

Gina Poe 41:50 Right, right, and trying to ascertain the life moving down deep in the depth of the ocean. (laughs)

Andrew Huberman 41:55 Yeah. Brace yourselves, uh, colleagues at Stanford Sleep Lab and elsewhere.

Gina Poe 41:58 (laughs)

Andrew Huberman 41:58 Uh, but please just tell us, 'cause I think w-... scientists want to know the truth.

Gina Poe 42:02 Yeah. I mean, it's not for nothing that you want to know what the cortex is doing.

Andrew Huberman 42:06 Mm-hmm.

Gina Poe 42:06 I mean, 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. And, um, but there's hope, uh, 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 sort of sub-cortical structures are doing, things like the absolute power of, 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, and vice versa.

Andrew Huberman 42:49 Mm-hmm.

Gina Poe 42:50 So, there is some hope, um, that we can gain from people with depth electrodes or animals, um, with depth electrodes that we could backwards, uh, machine learn what the cortex might be able to tell us about sub-cortical structures from the cortical EEG, so.

Andrew Huberman 43:08 Interesting. This is going to be a-

Gina Poe 43:10 Stay tuned. (laughs)

Andrew Huberman 43:10 ... a stimulu- yeah, stay tuned.

Gina Poe 43:11 (laughs)

Andrew Huberman 43:11 And this is going to be a stimulus for development of new technology-

Gina Poe 43:14 Yeah.

Andrew Huberman 43:14 ... which is always going to, uh, assist in scientific discovery.

Gina Poe 43:18 Yeah.

Andrew Huberman 43:18 Um,

Andrew Huberman 43:19 there's one more thing I wanted to ask about the architecture of the night's sleep.

Gina Poe 43:23 Yeah.

Andrew Huberman 43:24 Um, in terms of early part of the night.

Gina Poe 43:26 Mm-hmm.

Andrew Huberman 43:26 Earlier you mentioned the washout-

Gina Poe 43:28 Mm-hmm.

Andrew Huberman 43:29 ... of debris and-

Gina Poe 43:30 Mm-hmm.

Andrew Huberman 43:30 ... um, the so-called glymphatic system-

Gina Poe 43:32 Yeah.

Andrew Huberman 43:32 ... I think is what you're referring to.

Gina Poe 43:33 Mm-hmm.

Andrew Huberman 43:33 Could you tell us a little bit more about the washout that occurs in the brain during sleep.

Gina Poe 43:37 Yeah.

Andrew Huberman 43:38 What, what that is and what roles it's thought to serve?

Gina Poe 43:41 Mm-hmm.

Andrew Huberman 43:41 And perhaps if there are any ways to ensure that it happens or to ensure that it doesn't happen.

Gina Poe 43:46 Right.

Andrew Huberman 43:46 And obviously, we want this to happen.

Gina Poe 43:48 Yeah, yeah. Um, 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, and changed during sleep. Um, it unfolds. This process actually uses a lot of ATP, the power, um, structure, the fuel of the brain, and, uh, it unfolds also proteins while we're doing this, while we're using them. And so, during that first part of the night, uh, when we first fall asleep in the first 20 minutes or so, we're building that, uh, adenosine back into ATP and that's, uh, probably why power naps are called power naps because we're actually rebuilding the power. And then, um, 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, um, you know, need to be rebuilt when we're asleep because of its use during wakefulness. So, I liken that to, you know, 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, uh, slow wave sleep goes away. So, um, so what happens when a neuron is firing is that it expands, the membrane expands a little bit. It 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, it, the membrane expands a little bit as sodium brings water into the cell. Um, and then when they're silent, they contract. And so, in, 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 kind of like a bilge pump of the brain. So that can pump out ... Glia are also really important for this, um, in terms of cleaning up debris and transferring it to where it needs to go so, um, so I think of it actually as a bilge pump, um, cleaning out our brain.

Andrew Huberman 46:27 Interesting. I've heard about the glymphatic system-

Gina Poe 46:29 Yeah.

Andrew Huberman 46:29 ... and glymphatic washout. I've never thought about the mechanical aspects of it before.

Gina Poe 46:33 Okay.

Andrew Huberman 46:33 I always thought that for some reason, that now it's obvious to me there had to be something mechanical-

Gina Poe 46:39 Mm-hmm.

Andrew Huberman 46:39 ... but only now that you've e- e- educated me about this.

Gina Poe 46:41 Mm-hmm.

Andrew Huberman 46:42 I thought that for some reason the, 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.

Gina Poe 46:50 Mm-hmm.

Andrew Huberman 46:51 And pushing the fluid through-

Gina Poe 46:53 Yeah.

Andrew Huberman 46:53 ... cleaning out any misfolded proteins or-

Gina Poe 46:55 Mm-hmm.

Andrew Huberman 46:55 ... debris that might occur-

Gina Poe 46:57 Yeah.

Andrew Huberman 46:57 ... on the basis of these metabolic pathways.

Gina Poe 47:00 Yeah.

Andrew Huberman 47:00 And the consequence of that is to, uh, to what? To leave the brain in a state of, um, uh, more pristine action-

Gina Poe 47:09 Yeah.

Andrew Huberman 47:09 ... for, for the next day?

Gina Poe 47:10 Yeah.

Andrew Huberman 47:10 Is that right?

Gina Poe 47:11 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, you know? It's-

Andrew Huberman 47:19 Right.

Gina Poe 47:19 People have a harder time moving around and enjoying themselves and, um, if that builds up day after day, you know, it's going to be cognition, that would be the partygoers moving around, um, becomes hard. Yeah.

Andrew Huberman 47:33 And so this, um, bilge pump that you describe-

Gina Poe 47:36 Mm-hmm.

Andrew Huberman 47:36 ... is associated with the s- big slow waves of, of, um, deep, well-

Gina Poe 47:41 Yeah.

Andrew Huberman 47:41 ... of slow wave sleep.

Gina Poe 47:42 Yeah.

Andrew Huberman 47:43 Um, so this is going to occur more or less-

Gina Poe 47:44 Yeah.

Andrew Huberman 47:44 ... in the first third of the night?

Gina Poe 47:46 Yep.

Andrew Huberman 47:46 Is that right?

Gina Poe 47:46 That's right.

Andrew Huberman 47:47 And, um, are there things that inhibit this process and are there things that facilitate this process?

Gina Poe 47:54 Yeah. Uh, so, well one thing to inhibit is not to get it, um, (laughs) but-

Andrew Huberman 48:00 Right and here too-

Gina Poe 48:01 Yeah, yeah.

Andrew Huberman 48:01 Uh, sorry to interrupt-

Gina Poe 48:02 Yeah, go ahead.

Andrew Huberman 48:02 ... um, but it, and is this similar to the case with growth hormone where if you go to sleep later than you would normally-

Gina Poe 48:09 That's right.

Andrew Huberman 48:09 ... you miss the washout?

Gina Poe 48:10 You just miss it, yeah. It's not-

Andrew Huberman 48:11 You don't, it's not, you don't delay it.

Gina Poe 48:12 No.

Andrew Huberman 48:12 You miss, you miss the washout.

Gina Poe 48:14 That's right, that's right.

Andrew Huberman 48:15 Oh, boy.

Gina Poe 48:15 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 and REM sleep, not by slow wave sleep, so.... you need to, you need to get that first bit of sleep.

Andrew Huberman 48:27 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-

Gina Poe 48:32 Yeah.

Andrew Huberman 48:33 ... that, if that's their normal sleep cycle-

Gina Poe 48:35 Yeah.

Andrew Huberman 48:35 ... um, that-

Gina Poe 48:36 That should be okay.

Andrew Huberman 48:37 Okay.

Gina Poe 48:37 It should be okay.

Andrew Huberman 48:39 Yeah.

Gina Poe 48:39 Um, 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's shifted, good. Um, yeah.

Andrew Huberman 48:57 Okay. Yeah, there, there are a few studies I've, um, come across that really do argue for the fact that waking up circa sunrise-

Gina Poe 49:06 Mm-hmm.

Andrew Huberman 49:06 ... that doesn't mean at sunrise-

Gina Poe 49:07 Mm-hmm.

Andrew Huberman 49:07 ... but within an hour or two, maybe three hours of sunrise-

Gina Poe 49:10 Mm-hmm.

Andrew Huberman 49:10 ... and going to sleep within four hours after sunset or so-

Gina Poe 49:15 Mm-hmm, mm-hmm. Yeah.

Andrew Huberman 49:17 ... is actually better for the health of all human beings-

Gina Poe 49:20 Mm-hmm.

Andrew Huberman 49:20 ... than is being a night owl. And the night owl-

Gina Poe 49:23 Mm-hmm, yeah.

Andrew Huberman 49:23 ... there's almost like a night owl posse out there-

Gina Poe 49:25 Mm-hmm.

Andrew Huberman 49:25 ... especially on social media. They get very upset-

Gina Poe 49:28 Yeah.

Andrew Huberman 49:28 ... when you say that you should see morning sunlight-

Gina Poe 49:30 Mm-hmm.

Andrew Huberman 49:30 ... that after 10:00 AM-

Gina Poe 49:32 Mm-hmm.

Andrew Huberman 49:32 ... you kind of miss the boat.

Gina Poe 49:33 Mm-hmm.

Andrew Huberman 49:33 And they get very upset-

Gina Poe 49:34 Yeah.

Andrew Huberman 49:34 ... because I think there are about 20 or 30% of people perhaps who, um, who really feel like they function better staying-

Gina Poe 49:41 Yeah.

Andrew Huberman 49:41 ... up late and waking up late.

Gina Poe 49:42 Yeah.

Andrew Huberman 49:42 And they function much less well waking up early and going to bed early. But the data on health metrics-

Gina Poe 49:48 Yeah.

Andrew Huberman 49:49 ... suggests that, sorry night owls-

Gina Poe 49:51 Yeah.

Andrew Huberman 49:51 ... that they are wrong.

Gina Poe 49:52 (laughs) Yeah, sorry me 'cause I'm a night owl.

Andrew Huberman 49:54 Oh boy, okay.

Gina Poe 49:55 (laughs)

Andrew Huberman 49:55 Well then, I'm apologizing directly.

Gina Poe 49:56 No.

Andrew Huberman 49:56 And here-

Gina Poe 49:57 Do not apologize.

Andrew Huberman 49:57 ... I'm not a really early morning person.

Gina Poe 49:59 Yeah.

Andrew Huberman 49:59 I'm kind of more typical-

Gina Poe 50:00 Yeah.

Andrew Huberman 50:00 ... if, I wake up naturally around 6:30.

Gina Poe 50:02 Yeah.

Andrew Huberman 50:02 Somewhere between 6:30 and 7:30 AM.

Gina Poe 50:04 Mm-hmm.

Andrew Huberman 50:04 Go to sleep somewhere between 10:00 and 11:00 PM.

Gina Poe 50:09 Yeah, yeah.

Andrew Huberman 50:09 These are averages.

Gina Poe 50:10 Right.

Andrew Huberman 50:10 Um, 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 there too.

Gina Poe 50:24 No, 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 I, like you and like every human being on Earth do better if I go to bed earlier and wake up earlier. So one good thing for night owls is to have a child. (laughs)

Andrew Huberman 50:46 (laughs)

Gina Poe 50:46 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, uh, soon after your kids go to bed and wake up with them. That's the way to do it.

Andrew Huberman 51:17 Great. The child alarm clock.

Gina Poe 51:18 (laughs)

Andrew Huberman 51:18 Another reason to have children.

Gina Poe 51:20 Yes.

Andrew Huberman 51:20 Um, 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 riser, you know, 5:30 AM every morning, but I ended up getting a bulldog that would literally sleep 16 hours-

Gina Poe 51:36 Yes.

Andrew Huberman 51:36 ... if he could. A nuclear bomb could go off-

Gina Poe 51:38 (laughs)

Andrew Huberman 51:39 ... and he wouldn't wake up. But what I started to learn was that bulldogs actually have sleep apnea.

Gina Poe 51:44 Yeah.

Andrew Huberman 51:44 They're, it's a, as far as I know, they're the only species that has a genetically, um, they're essentially an inbred-

Gina Poe 51:51 Yeah.

Andrew Huberman 51:51 ... um, sleep defect.

Gina Poe 51:52 Yeah, yeah.

Andrew Huberman 51:52 And so I actually don't encourage people to get bulldogs because it's kind of a cruel breed.

Gina Poe 51:56 Mm-hmm.

Andrew Huberman 51:56 They suffer a lot in that body that they're born into.

Gina Poe 51:58 Mm-hmm.

Andrew Huberman 51:58 Anyway, um, a dog can accomplish some, some of this, but get the, get the, uh, the breed of dog that is going to-

Gina Poe 52:05 Wake up early.

Andrew Huberman 52:06 ... wake up early.

Gina Poe 52:06 Yeah.

Andrew Huberman 52:06 So in other words, don't get a bulldog or a mastiff.

Gina Poe 52:08 Well, you know, interestingly, all, all, um, predatory animals like dogs and cats and lions and us, um, well, more dogs, cats and lions than us, will, can sleep, you know, 16 hours a day. Uh, ferrets are predatory. They sleep-

Andrew Huberman 52:25 Oh, I had a pet ferret.

Gina Poe 52:25 Yeah.

Andrew Huberman 52:26 I used to... And, uh, sadly, I also used to work on ferrets.

Gina Poe 52:29 Yeah.

Andrew Huberman 52:29 Publish a number of papers.

Gina Poe 52:30 Yeah, yeah.

Andrew Huberman 52:30 Delightful animals.

Gina Poe 52:31 Yeah, and-

Andrew Huberman 52:32 Yeah.

Gina Poe 52:32 ... great because you can study development. It's really cool, um, because they're born very altricial 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, um, yeah, maybe we're not as predator, as much predators as we think because, in fact, we, our sleep is somewhere between the prey and the predators (laughs) -

Andrew Huberman 52:58 Hmm.

Gina Poe 52:59 ... in terms of the amount of sleep that we usually need a night. Um, but those predators can sleep 16 hours, um, napping all day long, and, and they're more crepuscular perhaps-

Andrew Huberman 53:09 Mm-hmm.

Gina Poe 53:09 ... like their prey are more.

Andrew Huberman 53:10 So dawn and dusk active?

Gina Poe 53:12 Yeah, yeah, yeah. Dawn and dusk active.

Andrew Huberman 53:14 Interesting.

Gina Poe 53:15 Um, yeah. But anyway, yes, uh, children and dogs. Actually, and if, 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, um, number three is children because, um, you know, when your children are young, but that only lasts a few years that they'll wake you up, um, when they're babies. Um, but the number one thing is pets (laughs) and pets needing to go out, um, 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 53:49 Another reason to not get a nocturnal pet.

Gina Poe 53:52 (laughs) Yes.

Andrew Huberman 53:52 People who get hamsters-

Gina Poe 53:53 Oh.

Andrew Huberman 53:53 ... pretty quickly realize that they are nocturnal-

Gina Poe 53:56 (laughs)

Andrew Huberman 53:56 ... and they want to run on their wheel around, so.

Gina Poe 53:57 Yeah, you got to put them in the living room away from where you sleep. (laughs)

Andrew Huberman 54:00 I vote fish tank folks.

Gina Poe 54:01 (laughs)

Andrew Huberman 54:01 Um, freshwater fish tank. There are all sorts of reasons to not get a saltwater tank. Freshwater fish tank.

Gina Poe 54:06 (laughs)

Andrew Huberman 54:07 (laughs) Um, or a child.

Gina Poe 54:08 (laughs) Yeah.

Andrew Huberman 54:09 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-

Gina Poe 54:16 Mm-hmm.

Andrew Huberman 54:16 They have very elaborate brain structures.

Gina Poe 54:18 Oh, yeah.

Andrew Huberman 54:18 Um, they're very smart.

Gina Poe 54:19 Yeah.

Andrew Huberman 54:20 Um, in the same family as the honey badgers and the other mustelids.

Gina Poe 54:23 Mm-hmm.

Andrew Huberman 54:23 Anyway, well, I, I shouldn't geek out too much on, on the mustelids, or else I'll take the, the remainder of all our time.

Gina Poe 54:30 (laughs)

Andrew Huberman 54:30 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.

Gina Poe 54:38 Yeah.

Andrew Huberman 54:38 And this is probably, um, the appropriate time for you to introduce us to this incredible structure in the brain, which is the locus coeruleus.

Gina Poe 54:46 Oh, yeah.

Andrew Huberman 54:46 A difficult, um, structure to spell-

Gina Poe 54:49 Mm-hmm.

Andrew Huberman 54:49 ... but a beautiful, a beautifully named structure.

Gina Poe 54:52 Mm-hmm.

Andrew Huberman 54:53 Um, I find locus coeruleus to be just fascinating, and I know, I, we know a small fraction of what it does, and I'm hoping you're going to educate me and, and our audience about, more about what it does, and hopefully tell us a little bit about its relationship to epinephrine, AKA adrenaline.

Gina Poe 55:09 Yeah. I'm so glad you brought this up because I can totally geek out on the locus coeruleus.

Andrew Huberman 55:14 Please do.

Gina Poe 55:15 (laughs) Um, locus meaning spot or place and coeruleus meaning blue, so you could just call it the blue spot. Um, that's the easiest. Every, um, animal with a brain has a blue spot, and, um, yeah, and I mean every animal with a brain because of course, uh, there are animals with nervous systems that are not centralized, like jellyfish. Um, but anyway, we're, we're digressing there. (laughs) So, um, the locus coeruleus is filled with neurons that have in them norepinephrine, which is the brain's version of epinephrine or adrenaline. It's also called noradrenaline. And what it does is it, just like adrenaline in 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. Um, and they will fire in a burst if, for example, if 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, um, and then tonic activity during the day when you're just, you know, doing your normal, going about your normal concentration kind of activity- activities is really good for, um, sustained attention. Um, it, it works with the cholinergic system of our basal forebrain, um, which is really important for learning and memory, also to help us learn about things and put things together. Um, but just tonic ale- levels are a signature of wakefulness and alertness. So too much is panic with the 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 come, goes from about on average, um, two hertz to about one hertz, one cycle per second, um, tonically. Um, 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, um, learned in the novelty encoding pathway in c- of our, 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, um, things all of our lives. So like erasing that RAM, um, or that, I don't know, what do you call those disks that you stick into computers that-

Andrew Huberman 58:05 Oh, uh, hard drive? Uh, no.

Gina Poe 58:07 Or you got a...

Andrew Huberman 58:07 Um, thumb drive.

Gina Poe 58:08 Thumb drives, yeah.

Andrew Huberman 58:09 Thumb drives.

Gina Poe 58:09 You're erasing your thumb drive so you, 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, a portant part of lifelong learning. Um, yeah. Uh, so much more I could say about that.

Andrew Huberman 58:43 Yeah. Locus coeruleus sounds fascinating.

Gina Poe 58:45 Mm-hmm.

Andrew Huberman 58:45 So it's connected to the basal forebrain cholinergic system.

Gina Poe 58:48 Mm-hmm.

Andrew Huberman 58:48 Um, the neurons in locus coeruleus, if I'm not mistaken, release-

Gina Poe 58:54 Norepinephrine.

Andrew Huberman 58:55 ... norepinephrine.

Gina Poe 58:55 Mm-hmm.

Andrew Huberman 58:56 Perhaps epinephrine as well?

Gina Poe 58:58 Uh, n- well, no, the brain's version of epinephrine is norepinephrine.

Andrew Huberman 59:02 Mm-hmm. Right.

Gina Poe 59:02 Um, the other thing it also, uh, the precursor to norepinephrine is dopamine.

Andrew Huberman 59:07 Mm-hmm.

Gina Poe 59:07 And so the source of dopamine in the hippocampus seems to be the locus coeruleus, and it's still a mystery as w- 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, um, and then there's also, um, galanin, which is important for releasing when we're stressed, and it helps also with that rapid learning. Um, it works in concert with norepinephrine in, in doing what it needs to do to strengthen synapses so that we learn really quickly.

Andrew Huberman 59:47 I, I love, um, that there are multiple molecules involved because that signals us to a principle which is that even if people can't remember all, all the names-

Gina Poe 59:58 Mm-hmm.

Andrew Huberman 59:58 ... um, that rarely in biology is something handled by just one molecule or pathway.

Gina Poe 1:00:04 That's right.

Andrew Huberman 1:00:04 That redundancy is the rule-

Gina Poe 1:00:05 Yeah.

Andrew Huberman 1:00:06 ... because signaling attention to specific events is so important.

Gina Poe 1:00:11 That's right.

Andrew Huberman 1:00:11 So that, um, I'm going to use that as a just-so story.

Gina Poe 1:00:14 Yeah.

Andrew Huberman 1:00:14 I always say, you know, I wasn't consulted at the design phase-

Gina Poe 1:00:16 (laughs)

Andrew Huberman 1:00:17 ... but it makes sense to me as to why redundancy would exist in the system.

Gina Poe 1:00:20 Absolutely, and in fact, when we form hypotheses about the brain w-We're always wrong. And the reason why we're always wrong is 'cause 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, you know, the glia, the neuropeptides, the neurotransmitters, the physical structure of synapses. And so when I was going through grad school 35 years ago, uh, w- we, the dogma was that every neuron contains one neurotransmitter and releases one neurotransmitter and you had excitatory neurotransmitters and inhibitory neurotransmitters and neuromodulatory neurotransmitters, but that's as complicated as it got. And then we fo- started talking about neuropeptides and people said, "Oh, no, please don't," (laughs) "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 1:01:11 And maybe even hormones too.

Gina Poe 1:01:12 And hormones and, oh, Lord, you know? It's just-

Andrew Huberman 1:01:15 Yeah.

Gina Poe 1:01:15 ... so complicated, but, I mean, gotta 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 w- if the way I hypothesized it, with it." You know, we actually need redundancy. We need all of these systems to work together.

Andrew Huberman 1:01:32 Yeah, it's, um-

Gina Poe 1:01:33 (laughs)

Andrew Huberman 1:01:33 ... it's, uh, daunting sometimes, but it also ensures many, uh, many careers in science-

Gina Poe 1:01:38 (laughs)

Andrew Huberman 1:01:38 ... and neuroscience in particular. So, um-

Gina Poe 1:01:40 Yeah.

Andrew Huberman 1:01:40 ... uh, note that, uh, aspiring scientists, there's plenty of room, uh, for discovery.

Gina Poe 1:01:46 Do you want me to talk about norepinephrine and-

Andrew Huberman 1:01:48 Yeah. So what I'd l-

Gina Poe 1:01:48 ... emotion and-

Andrew Huberman 1:01:49 Yes. Well, what I'd love-

Gina Poe 1:01:51 ... stress? (laughs)

Andrew Huberman 1:01:51 ... what I'd love for you to, um, tell us about is, you know, what role this lack of norepinephrine release during rapid eye movement sleep-

Gina Poe 1:01:59 Yeah.

Andrew Huberman 1:02:00 ... um, is thought to achieve and w- maybe you could also review some of your work describing conditions under which norepinephrine invades-

Gina Poe 1:02:09 Yeah, invades sleep.

Andrew Huberman 1:02:10 ... uh, rapid eye movement sleep and other patterns of sleep and how that can be detrimental.

Gina Poe 1:02:14 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, um, schema from which the h- hypotheses come, but one thing that happens to people with post-traumatic stress disorder is that there's a lot of evidence that the locus coeruleus doesn't stop firing in REM sleep. So whereas their, um, levels of norepinephrine might be similar to people without PTSD during the day and even during the first part of the night, um, during the wee hours of the morning and when you measure norepinephrine levels from metabolites, um, in the blood or the s- cerebral spinal 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 l- locus coeruleus is not shutting down during REM sleep like it should. Other evidence is heart rate variability. When our locus coeruleus is firing, um, 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, our norepinephrine levels are lower. During REM sleep, that goes away entirely and our heart rate is, is, um, is, um, dominated by, uh, parasympathetic rather than sympathetic activity and also what our brain is driving, you know, what are we dreaming about, for example. If we're dreaming we're running, our heart rates will go up. But norepinephrine levels sh- still should be low or off. So, um, people with PTSD that noradrenergics, uh, we're studying these in rats too. Is it true that our locus coeruleus doesn't, uh, 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, um, norepinephrine would act at synapses to prevent that, uh, weakening that you really need, for example, of novelty in coding structures and it keeps memories in that novelty in coding 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, and it's that thumb drive, um, we, we need it to be erased so that we can learn new things, uh, once it's been consolidated to the w- the hard drive of our cortex and if, so if we're not able to do that, we fill up that RAM, um, 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've consolidated that traumatic memory to the cortex you need to erase it from the novelty in coding 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, um, 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, like earlier that same day, and, um, respond as you would to, uh, uh, an early, uh, a recent trauma, which is with beating heart and all of that. Um, so even memories that are years past, if you're never able to downscale that novelty in coding structure and you purge it from that traumatic memory, it will stay fresh and new and then become maladaptive.

Andrew Huberman 1:06:13 I'd like to just take a brief moment and thank one of our podcast sponsors, which is InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that blood work is the only way that you can monitor the markers, such as hormone markers, lipids, metabolic factors, et cetera, that impact your immediate and long-term health. One major challenge with blood work, however, is that most of the time it does not come back with any information about what to do in order to move the values for hormones, metabolic factors, lipids, et cetera, into the ranges that you want. With InsideTracker, changing those values becomes very straightforward because it has a personalized dashboard that you can use to address the nutrition-based, behavior-based, supplement-based approaches that you can use in order to move those values into the ranges that are optimal for you, your vitality, and your longevity. InsideTracker now includes a measurement of apolipoprotein B, so-called ApoB, in their ultimate plan. ApoB is a key marker of cardiovascular health, and therefore there's extreme value to knowing your ApoB levels. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman to get 20% off.

Andrew Huberman 1:07:31 What approaches are you aware of that can, um, 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?

Gina Poe 1:07:46 Mm-hmm.

Andrew Huberman 1:07:47 Um, y- we've had a couple podcast episodes, solo episodes and with guests, talking about trauma. We had Dr. Paul Conti-

Gina Poe 1:07:53 Mm-hmm.

Andrew Huberman 1:07:53 ... who's a Stanford-trained, Harvard-trained, um, psychiatrist who talked a lot about trauma, wrote an excellent book on trauma and, um-

Gina Poe 1:08:00 Yeah.

Andrew Huberman 1:08:00 ... certainly sleep was emphasized as a, as a key thing, like get enough sleep.

Gina Poe 1:08:04 Mm-hmm.

Andrew Huberman 1:08:04 But here you're saying even if somebody with trauma gets enough sleep, if locus coeruleus is hyperactive during sleep-

Gina Poe 1:08:10 Yeah.

Andrew Huberman 1:08:10 ... 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.

Gina Poe 1:08:19 Yeah.

Andrew Huberman 1:08:20 Um, nowadays there's a lot of interest and attention on, um, clinical studies on exploring psychedelics-

Gina Poe 1:08:26 Yeah.

Andrew Huberman 1:08:26 ... high dose psilocybin and MDMA.

Gina Poe 1:08:28 Yeah.

Andrew Huberman 1:08:29 The, so there's a vast landscape-

Gina Poe 1:08:30 Yeah.

Andrew Huberman 1:08:31 ... none of which, as far as I know, is really focused on sleep specifically.

Gina Poe 1:08:34 No, they're not. And they should be, because actually psychedelics is a sleep-like state.

Andrew Huberman 1:08:40 Mm-hmm.

Gina Poe 1:08:40 And, um, it's a REM sleep-like state, although of course there are some major differences. So yeah, (sighs) so much to talk about here. So antidepressants, um, 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. Um, and if you're able to get REM sleep, it would probably be REM sleep with some noradrenergic-

Andrew Huberman 1:09:07 Mm-hmm.

Gina Poe 1:09:07 ... activity. So actually I think, anyway, I'm not a physician, that, um, 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. Um-

Andrew Huberman 1:09:30 Is that statement-

Gina Poe 1:09:31 Yeah.

Andrew Huberman 1:09:31 ... specific to antidepressants that, um, tickle the noradrenergic pathway? So-

Gina Poe 1:09:35 Yeah.

Andrew Huberman 1:09:35 ... the, the one that comes to mind is, um, bupropio- I can never pronounce it, bupropion which is-

Gina Poe 1:09:40 Yeah.

Andrew Huberman 1:09:40 ... uh, what, uh, I think the brand name is Wellbutrin.

Gina Poe 1:09:42 Yeah.

Andrew Huberman 1:09:42 It's a dopaminergic and noradrenergic agonist.

Gina Poe 1:09:45 Mm-hmm.

Andrew Huberman 1:09:46 So that's the net effect-

Gina Poe 1:09:47 Yeah.

Andrew Huberman 1:09:47 ... as opposed to the Prozac, Zoloft variety, which are SSRIs.

Gina Poe 1:09:51 Yes. Yes. But (laughs) SSRIs themselves also are problematic because we didn't talk about it yet, but the dorsal raphe nucleus, which produces serotonin, which the specific s- serotonin, specific serotonin reuptake inhibitors block from being reuptaken, um, leaves too much serotonin out there. And what serotonin also is another noradrenergic, I mean, sorry, another neurotransmitter that's downregulated during REM sleep, that's-

Andrew Huberman 1:10:18 Hm.

Gina Poe 1:10:18 ... 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 sort of weights, um, our brain away from a sense of familiarity and toward novelty. And, um, it might be one reason why it's an effective, uh, antidepressant, because it makes the world feel fresh and new again, right? Um, but y- you, when you have too much, you're holding a novel traumatic memory, um, 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 1:11:12 It's really interesting, um, we hear a lot about serotonin and, uh, it's not often discussed in terms of its features related to novelty enough, I think.

Gina Poe 1:11:21 Mm-hmm.

Andrew Huberman 1:11:22 Um, and what you just described, um, cues me to something that, uh, Dr. Paul Conti and others have, have said in terms of trauma, and here I'm paraphrasing, so my apologies to them for not getting this exactly right-

Gina Poe 1:11:32 It's okay.

Andrew Huberman 1:11:32 ... that, 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-

Gina Poe 1:11:45 Mm-hmm.

Andrew Huberman 1:11:46 ... to eventually just become kind of a boring old story.

Gina Poe 1:11:50 Mm-hmm. Mm-hmm.

Andrew Huberman 1:11:50 That has kind of a fuzzy texture-

Gina Poe 1:11:52 Mm-hmm.

Andrew Huberman 1:11:52 ... as opposed to this kind of sharp-

Gina Poe 1:11:55 Yeah.

Andrew Huberman 1:11:55 ... um, high friction texture that invades our thinking-

Gina Poe 1:11:58 Yeah.

Andrew Huberman 1:11:59 ... um, and obviously our sleeping states as well.

Gina Poe 1:12:01 Mm-hmm.

Andrew Huberman 1:12:01 So, um, again, uh, and, uh, I appreciate the disclaimer, the caveats around, you know, not being a clinician, et cetera-

Gina Poe 1:12:08 Mm-hmm.

Andrew Huberman 1:12:08 ... but I do think that there's a lot of interest now in whether or not antidepressants are effective for trauma or not-

Gina Poe 1:12:13 Mm-hmm.

Andrew Huberman 1:12:13 ... and I think these, these aspects of neuromodulation-... as they relate to, um, let's call it erasing traumas or changing the emotional load of traumas during sleep, um, is something important to take note. We also have a lot of clinicians that listen to this podcast, so they should also take note-

Gina Poe 1:12:27 Yeah.

Andrew Huberman 1:12:28 ... um, please.

Andrew Huberman 1:12:29 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-

Gina Poe 1:12:42 Yeah.

Andrew Huberman 1:12:43 ... um, and allow late stages of sleep each night to have their maximum positive effect-

Gina Poe 1:12:49 Mm-hmm. What do you do?

Andrew Huberman 1:12:50 ... is there anything that I can do besides avoiding, um, avoiding traumas, avoiding serotonergic or noradrenergic compounds?

Gina Poe 1:12:58 Well, I would also avoid anything just prior to going to sleep that might excite those systems.

Andrew Huberman 1:13:04 Hmm.

Gina Poe 1:13:04 So, a lot of novelty. Um, a lot of, you know, exciting, um, stress-inducing video games. Um, 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, um, we haven't been able to test this with rats because we can't ask them to do a deep breathing exercise (laughs) . Um, there might be a way we can do that, but I haven't found out or figured it out yet. Um, but if there's a way you can make your sympathetic system, nervous system calm down before you go to sleep, it might be for you meditation or deep breathing exercises. It might be for some a warm bath or a comforting book. Nothing too exciting, but, um, also nothing too boring perhaps. Um, 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, um, you're hyped up, then your sleep could become maladaptive. Um, another thing that happens in rats that we have yet to know if it happens in women is that female rats have, uh, three phases of their estrus cycle that, um, 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, um, one thing that might work, and in fact there are a few studies that show it, it could work really well, is, um, uh, giving women after a trauma event, um, something that contains estrogen because estrogen somehow is protective against PTSD and they know that through retrospective studies where they, uh, gave women in emergency room either a pill with estrogen in it 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, um, there are some 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. Um, but there's something about estrogen that's really helpful and protective about, uh, that from, 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, um, we are looking into it actively right now, but it's, uh, 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 the locus coeruleus during sleep in women, um, that, 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, in helping women be more resilient to stress-related, uh, disorders.

Andrew Huberman 1:16:22 What are some other, um, sex differences as they relate to sleep?

Gina Poe 1:16:26 Yeah. Yeah, that's a really good question. There have been very few studies unfortunately, uh, of women and sleep. Um, women and estrus cycle or menstrual cycle and sleep and, um, but what we have found which actually largely replicated a study in 1960, um, is that, 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 it's, those sleep spindles are more dense and more coherent across the brain areas. The theta cycle which is five to 10 hertz in the hippocampus important for when you're learning and also important during REM sleep. It is also bigger and juicier, um, during the high hormonal phases. So even though there's less sleep, it's more efficient and better. Um, but, uh, so, so all of that efficiency seems to be reduced in those other hormonal phases. Um, so even though you might sleep a little more, um, you might need more sleep in fact in order to accomplish the same thing that you can get with that short, um, very efficient sleep of high hormonal phases.

Andrew Huberman 1:17:54 Very interesting.

Gina Poe 1:17:55 Yeah.

Andrew Huberman 1:17:55 I think, um, there is a growing trend at least among, uh, NIH-funded grants to, uh, require, um, that, uh, as they refer to it in the grants, biological sex as a variable.

Gina Poe 1:18:07 Yes.

Andrew Huberman 1:18:08 Uh, and again, here we're ta- not talking about sex the, um, the verb, although I'm sure there are