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 integrated, 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.
An 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
Is 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.
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, 8 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 releasing 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 is Doctor Paul explains their critical brain sir.
It's an endocrine, that is hormone circuits that regulate, not just the duration in 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
Is episode dr. Gina Poe shares critical information about, not just Neuroscience, but physiology, and the hormone systems of the brain and body. That strongly, inform mental health, physical health, and performance. So by the end of today's episode, you'll be far more informed about sleep and how it works. The different roles, it performs, and you'll have several new actionable steps that you can take in order to improve your mental health, physical health, and performance. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire.
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 element element 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, the electrolytes are critical to the function of every cell in your body, in particular, the neurons, the nerve cells. So I've talked about before on this podcast neurons nerve cells,
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Welcome, thank you. I've really been looking forward to this conversation because I'm familiar with your work and I know that many people are going to be excited to learn about your work, as it relates to sleep, as it relates to problem, solving creativity addiction, and craving relapse, and a number of other important topics. So to start things off, I would love for you to educate us a bit about this thing that we are all familiar with and yet very few of us understand which is sleep.
And if you would, could you describe the various phases of sleep, that exist? What distinguish them and perhaps frame, this within the context of what would a perfect night sleep? Look like, okay, how long would it last more or less? And what would the biology look like, what? What is a perfect night
sleep? 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.
Our brain chemistry is completely different. And in the different stages of sleep, which there are is. Non-rem and REM are the two major states of sleep. And every animal we've studied so far, seems to have both of those States. Anyway, those two states are entirely different from one another to, and even with in non-rem, there are three states stage one, which is what you slip into. When you first falling asleep, it's dozing. There's kind of an interesting Rhythm that goes on in the brain is 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 3 slow-wave sleep, which is the most impressively different and then and between that and REM sleep. So, stage 2, I'll talk a little bit more about and then the Deep slow-wave Sleep state which is when big slow, wave sweep through our brain and now we realize that it cleans our brain. One of the things that those big slaves do is cleans our brain and does other
Really important things to restore us from a day of wakefulness and then REM sleep, which is the most popular because that's where we have the most active dreams. And when you wake up, someone out of REM sleep, they'll almost always report having dreams, something really bizarre. That's called REM sleep, rapid eye movement sleep. So those are the four states of sleep, human sleep. And we cycle through them every 90 minutes or so. When we go to sleep, say 10:00 10:30 11:00.
Our first REM sleep period comes about 105 minutes after we fall asleep and lasts about 20 minutes actually, it comes about 95 minutes and last 10 or 15 minutes. And then, we start over again, and we have about five of those per night for a perfect night, sleep for 5, something like that. So a perfect night sleep is seven, half eight hours. There was a really great study that put people in a semi
Can dream 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 twelve and then they leveled off after a week or two to about eight hours and 15 minutes of sleep. So you actually can't oversleep. I mean they had nothing else to do but sleep and they would round off to on average eight hours and 15 minutes a night. And then the spend the rest of the time, twiddling their thumbs humming
Tunes daydreaming,
I want to get back to the Contour of a perfect night sleep. But I'm intrigued by this idea that people can't oversleep. I'm often asked whether or not we can get too much sleep. And whether or not sleeping to log long, scuse me can make us groggy the next day, is there anything to that? And how does one, determine how long they should sleep right on average on
average? Yeah. Well, that's interesting because different people need seem to need different amounts of sleep, but we don't really even
I know exactly what sleep is for. So, what they need is, you know, kind of, its, you know, Mercury Marquis. So, we do know a lot of things that sleep does now for us. But we don't know how long those things take. So, how long we need to sleep is also just a big question mark. But some people don't feel rested until they slept nine hours. And some people don't feel rested after three or four and a half, but
Most people, if they consistently deprive themselves of sleep, so that they're only sleeping for four and a half hours a night, build up cognitive deficit that just builds up over time. The more nights, you have with sleep deprivation, the more cognitive deficit you have. And so, you need sleep again to sleep more to recover. Now, the question you had about you over and you oversleep, right,
sleep, to the point where it's too much, you know, that we growing up.
When I was in high school, my girlfriend's dad had this belief that no one should sleep in past 6 a.m. So he would wake all the, there were two children at home, he would wake up the kids in that house. He had to sing Against oversleeping. Regardless of when people went went to sleep and I was thought that was an interesting mentality.
Terrible actually. Because what that will do is it will put you make you sleep, your the next night to get to bed on time so it'll build up your homeostatic need if you wake
Wake up too early but so I don't think you can oversleep. But people who sleep a lot. Like people who sleep over 9 hours, it's probably indicative of some other problem. Because, in fact, if you have a lot of different conditions, it will cause you to sleep a lot more. Probably because what it does is it interferes with your efficient sleep, the efficiency of your sleep. So if you find yourself sleeping consistently 9, h, plus every night, then you might want to consult a doctor about maybe.
Else. It might be, it could be cancer. It could be sleep. Apnea batches affects a lot of people. It could be that your sleep is super inefficient because you're snoring a lot more than, you know, or you're waking up a lot more than, you know, every night. So you might want to sleep study just to see how your sleep is, and then see what else might be causing you to sleep so much.
And that wouldn't be. If somebody is sleeping 9 or 10 hours, you know, every once in awhile, you mean if they're consistently sleeping from,
More than
nine hours feel like they needed in order to function cognitively. The next day, it might be that your sleep is just not efficient and you might want to look into why that's the case,
interesting? Forgive me for the anecdote, but I can't resist years ago. I went to an acupuncturist and he gave me these red pills of which I don't know what they contained. But I took them because he told me they would help with my sleep and I would fall asleep about 30 minutes after taking them, and I would have a
Crescent. Incredibly scuse me vivid dreams and I'd wake up for five hours after having gone to sleep, feeling completely rested, something that I've never really experienced testing on a consistent basis. I want to do mass spec on these pills. I still have no idea what was in them
whatsoever. Exactly. Some
people thought that perhaps they had GHB gamma hydroxybutyrate, which is, by the way, an illegal drug, it can kill you. It's not a, not something you want to take. But anyway, if ever, someone can figure out what the red pill,
Those were, I'll be very, and this is not a red pill of the, of the other sort red pill. This is just the red sleep pills,
could have been even a placebo effect because for cbo's extremely strong.
So although I don't know, there was really something to these red. So shout out to the acupuncturist and, and the Eastern medicine, but to return the site to this idea of the architecture of a perfect night sleep. So you said, we fall asleep. The first 90 minutes,
Sleep. REM sleep. Rapid eye movement, sleep will arrive at about 95 minutes in. Does that mean that the rest of that 90 minutes is consumed with slow-wave sleep?
Yeah. Non-rem
sleep. Okay. What about the Sleep? Where we are lightly asleep? And we might have a dream that has us somehow thinking about movement or that we jolt ourselves awake. That often happens early in the night.
Yeah, that's the first stage stage, 1 and Stage 2 sleep and Stage 2 sleep.
Is really cool because that has something called sleep, spindles and K complexes. And what sleep, spindles are a little bit of activity, that's 10 to 15 Hertz in frequency. It's a conversation between the thalamus and the cortex. The Gap Thalamus is the gateway to Consciousness and the neocortex, you know, processes, all our cognition. And 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 it during while we're falling asleep. On the reason we call it falling asleep is because in stage, 1 and Stage 2, our muscles are relaxing and if there's part of our brain, that's conscious enough to sort of recognize that relaxation will feel like we're falling and will jerk awake. So often that hallucination.
And it's called hypnagogic. Hallucination will feel like it'll be include some falling aspects that will wake up out
of. That's really interesting to me. I've long felt that sensation of almost like, dropping back into my head. Mmm, so much. So that if I elevate my feet, just slightly and I tilt my head back, just slightly in order to go to sleep. I find I fall asleep much, much faster, but it does feel as if I'm going to fall like almost going to do a backward somersault actually really like the sensation and
Really because it proceeds falling deeply
as. Yeah, that's really interesting. I'm somebody has to do a study of elevated
feet and yeah there and there's a little bit on body position and sleep and some of the washout that we'll talk about. So, early in the night, you got these lighter stages of sleep less rapid eye movement, sleep. What can we say about the dreams that occur during the say first and second, you know, 90-minute cycles of sleep? Are they quite different than the patterns of sleep?
And dreaming that occur later in the night or toward
morning. Well, okay, that's an interesting question. There's a lot of facets to it. There is some evidence that the first four hours of sleep are very important for memory processing. And in fact, if you learned something new that day or have experienced a new sensorimotor experience, then you're early sleep, dreams will incorporate that experience.
More than the later sleep dreams later, is that memory gets Consolidated from the early structures, which are the hippocampus deep in the temporal lobe to the cortex in a distributed fashion. That memory seems to move from that hippocampus to the cortex. And also the dreams that incorporate that memory also move later in the night, so nobody knows why but it does. There was a great study by Sadako Ribeiro who
Who studied the consolidation of memories from the quartet from the hippocampus to the cortex in a rat across the period of a full day. Sleep because rat sleep in the day time and he found that each subsequent rims sleep period moved that memory from the hippocampus to the first area that projects to it and then the second area and then the third area. And you can see the memory moving through the throughout the Sleep. Cool period.
Yeah, very cool.
Have to read that study. So there's a number of different hormones associated with the different stages of sleep. We know that melatonin is a hormone that time of night time. That makes us sleepy. What about growth hormone release, when does that occur during
sleep? So growth hormone release happens all day long, and all night long, but the deep slow-wave sleep, that you get the very first sleep cycle is when you get a big bolus of growth hormone release and in men and women,
And 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 cost the day just as much overall growth hormone release, but endocrinologist will tell you that big boluses do different things than a little bit eked out over time. So that is well, we know there's also a big push to synthesize proteins. So that's when
The protein synthesis part that builds memories for example, in our brain happens in that first cycle of sleep. So you don't want to miss that, especially if you've learned something really big and needs needs more synaptic space to encode.
It, how would somebody miss that first 90 minutes
driving themselves? Yeah, so
so let's say, I normally go to sleep at 10 p.m. and then from 10 to 11:30 would be this first phase of sleep. And that's when the growth hormone big,
Bolus of growth hormone would be released. Does that mean that if I go to sleep instead at 11:30 or midnight that I missed that first phase of sleep? Yeah. Why is it not the case that I get that first phase of sleep? Just simply starting later. It is 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 Circ antique circadian clocks are synchronized. And so, our cells are ready.
Respond to that growth hormone release at a particular time and if we miss it and it's a time in relation to melatonin also. So if you miss it, yeah, you might get some growth hormone release, but it's occurring at a time when that your clock is already moved to the next phase and so it's it's just a clock thing.
Yeah, I don't think we can overstate the importance of what you just described and to be honest, despite knowing a bit about the Sleep research and circadian biology, this is the very first time that I've ever heard.
Add 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. Yeah that's incredible. And I think important and as many listeners are probably realizing also highly actionable. So what this means is that we should have fairly consistent bedtimes in addition to fairly consistent. Wake times that,
right? Exactly. And in fact, one of the best markers of good
Health when we get older is consistent bedtimes.
Wow, okay. I don't want to backtrack but I did write down something that I think is important for me to resolve or for you to resolve. So, I'm going to ask this people that sleep nine hours or more, perhaps that reflecting in issue, some underlying issue perhaps is being a teenager or an adolescent and undergoing a stage of development where there's a lot of bodily and brain.
And growth and exception to that because yes, I don't recall sleeping a ton. When I was a teenager, I had a ton of energy, but I know a few teenagers and they sleep a lot. Yeah, but they'll just sleeping sleeping, sleeping sleeping. Should we let them sleep and sleep and sleep, okay? Sleep. Okay, so that's the one exception. What about
us, baby's? Okay, when he, 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 I 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 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 p.m., are there things that I perhaps do in the preceding hours of the preceding day?
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 alcohol definitely will do that because alcohol is a REM sleep suppressant and even suppresses some of that stage to transition to REM with those sleep spindles and those sleep spindles we didn't talk about their function yet but they're really important for moving memories to our cortex. It's a unique time when our hippocampus the sort of like the ram of our brains, writes it to a
Disc and which is the cortex. And there is 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 is also a part of the consolidation process and 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
badly. It's probably fair to say no ingestion of alcohol within the
Four to six hours, preceding sleep, given the half-life, give it power at all or at all would be better. But I know some people refuse to go that way
maybe a little bit is okay. I don't know what the dose response is but there are studies out there. You can look
at great. So we're still in the first stage of sleep and I apologize for slowing us down, but it sounds like it's an incredibly important. First phase of sleep. What about the second and third, 90-minute blocks of sleep? Is there anything that makes those
Unique. What what is their signature besides the fact that they come second and third in the
night? There's more and more, REM sleep, the later, the night we get, there's also a change in hormones, you know, the growth hormone and melatonin levels are starting to decline but other hormones are picking up. So it is a really different stage that you also don't want to shortchange yourself on and I think that's the stage. Many studies are showing that those are the times and sleep.
When the most creativity can happen, that's when our dreams can incorporate and put together old and new things together into a new way. And and our schema are built during that time. So yeah, we can change our minds best during those phases of sleep. Could
you elaborate a little bit more on schema? No one. I don't think anyone on this podcast is ever discussed schema. I'm a little bit familiar with schema, from my courses on psychology, but it's been a while, so maybe.
Just refresh my mind and everyone everywhere,
it's still a concept or came out is how do you defend right? I think of schema as like we have a schema of Christmas right. We had when we have all kinds of ideas that we sew together and call Christmas and 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 have normally associate with Christmas presents, family gathering. When it is all of this stuff is sewn together into one. There's a thread linking them all and we can just give ourselves a list of words and and none of them contain the word Christmas. And then ask people later, you know, give them another list of words and include the word Christmas. And they'll say, oh yeah, that word was there. Because in their minds, they brought up that word Christmas because it's part of that whole schema. So that's what it's sort of.
A related lot of related Concepts I guess
I think about its or like on the desktop of my computer would scare some people but it's just a ton of folders. Yeah, but each of the folder names mean something very clear and specific to me. And inside of those, folders, are collections of things that make sense, in terms of how their batch is, that kind of one way
to think about, you know, 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 Ram, that's when your computer of your
Rain is opening folders and comparing document seeing if it. Is there anything the same these two documents look, very much the same, but there's a little bit of difference and it can 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 in strengthen it if it you know, makes your schema interesting and different
very interesting. Many people including myself
Tend to wake up maybe one string, the middle of the night to use the restroom. I've tried to drink less fluid before going to sleep. I've I've heard also that the impulse to urinate forgive the topic but a lot of people deal with this. So the impulse to urinate is also dictated by how quickly you drink fluid, not just the total volume. So I've switched to sipping fluids more slowly for my last beverage of the day which seems to help. But the point here is that, I think a lot of people wake up once in the middle the night, oftentimes to use the restroom but oftentimes just
Around 3:00 a.m. and might be up for a few minutes. Hopefully, not on their phone or viewing, any Bright Light, which can cause more wakefulness. But then go back to sleep. Is there any known detriment to this middle of the night waking? Or should we consider it a normal feature, for some people's
sleep architecture? I think we shouldn't worry about it, actually. I think, you know, sleep is really incredibly well homeostatic, lie regulated and so really don't worry about how much you're sleeping. As long as you're not intentionally depriving yourself
Sleep by doing something really rewarding and exciting because even that is stressful to your body and deprives you of a lot of things were talking about. So don't worry about it. It's absolutely normal to wake up at least, once in the middle of the night to go to the bathroom. And as long as you can get back to sleep in a reasonable amount of time, 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.
We're going to bed a little earlier,
so if I understand correctly there's a little bit of asymmetry to sleep. That catching that first phase of sleep. It's like you either get it or you don't and you have to get it by. Going to sleep. Yes. Actually the same time your site may be plus or minus 15 minutes or so. Yeah. 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? Yeah. Yeah. Yeah. And and we don't know actually the answer to whether or not the sleep in the middle.
Between that early sleep in 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.
Well, I suppose I am the experiment in that case because I do tend to wake up once per night and I've sort of come to recognize it as part of my normal, sleep architecture. I don't obsess over it. I do notice that when I go back to sleep and especially toward morning that my sleep is incredibly deep, my dreams are
Bleah Vivid that's I don't always remember them. But what is unique? Perhaps about the architecture of dreams and sleep. In the, let's say, the last third of the night or those or the second half of the
night, right? Yeah. And the second half the night we have longer, REM, sleep periods and those are considered the deepest sleep even though slow wave sleep big slow, wave is considered deep. It is
deep but I called slow-wave sleep deep sleep and REM sleep rapid I'm in. But now you're telling me that REM sleep is actually the deeper sleep. Okay.
There needs to be a new nomenclature sleep researchers deeper. No, no,
please, the reason why he called slow-wave sleep, deep sleep is because it's difficult to arouse people out of that state. And when you do, arouse them out of that state there must 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 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 and we're rapid eye movements, more dense and often people will incorporate that sound into their
dreams. Hmm. So the body and brain are somehow conscious of the of the
Mound and I've heard also smells can even make it into our dreams and REM sleep, but that we, it doesn't Rouse us. It does
arouse us as often. Yeah. 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. This low waves aren't as large, which is probably problematic, but we are not sure. And so then REM sleep becomes the deepest stage actually.
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 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 alarm so that instead of something that the kids don't associate with anything like the real, 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. I don't know. Having carried sleeping children in from the car. I don't know that I want children to start waking up from sleep because that's one of the best things when we get home and the kids are asleep in the back seat, you can literally throw them over your shoulder. Gently, of course, yes. And put them to sleep in and it they are completely out. Yeah, it is wonderful. One of Nature's gifts, I'd like to take a quick break and acknowledge one of our sponsors. Athletic greens, athletic greens. Now called a G1 is
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Again, that's athletic greens.com huberman to get the five free travel packs and the year supply of vitamin D3 k 2. So this enhanced volume or proportion of rapid eye movement, sleep in the second half of the night relates to more elaborate dreams. We are paralyzed during REM sleep.
Correct? Yes. Normally to paralyze. And that's really good because that's the time when we're actively dreaming, storyline dreams and we could hurt ourselves. We are actually
They really cut off from the outside world in terms of, you know, responding to say this table or window or a door. And so different from sleepwalking, which is out of slow asleep and out of slow asleep. At sleepwalking is a mixture between sleep and wakefulness, so you actually will respond to the door. You can cook a full meal, drive your car while you're in. Deep slow-wave Sleep, it's scary because you never know what you're going to do. You don't have voluntary involuntary control
all over it. You have no conscious control of it, but you can actually safely navigate some situations in sleepwalking and actually have a conversation, although it may not make much sense when you're sleep talking in REM sleep, you're not processing the outside world, and instead, when you're acting out your dreams, you could be doing things, like, walking through a plate glass window or falling off of, you know, down the stairs, things like that. So, you really
Watch your muscles to be inactivated during REM sleep. Otherwise, you will act out those dreams and really hurt yourself, or your bed partner.
What about sleep, talking, we're talking in sleep. I don't know how many relationships have been saved by sleep talking, but I'm guessing a few have been destroyed, and I'm guessing that talking in sleep, could have meaning, or perhaps has no meaning, just as dreams could have meaning, or no meaning, as we recall
them. Yeah, do not take sleep talking, seriously.
SLI, 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 just saved. A number of
relationships that I'm not directing this at anyone in particular, but I guarantee you just did noted. So as people start to approach morning or the time when they normally would wake up,
I've heard that it's important to if possible complete one of these 90-minute Cycles prior to waking up. That is if you set your alarm for halfway through one of these 90-minute cycles that come late in the night of sleep, that it can lead to rather groggy patterns of waking. So I'll just ask you directly. Do you use a an alarm clock? I do. Not thankfully. I'm in a line of work that doesn't require me normally to do anything at any
Regular time, I'd do it when I do it, unless I have to catch a plane and then I always set my alarm just in case.
Well, as a fellow academic, I can tell you, there are plenty of punishing features about being an academic scientist that that offset the fact that you don't have to use an alarm clock, but it is nice that you can often say your own schedule. So would you recommend that if possible that people not use an alarm
clock? Yeah, absolutely. If you can just listen to your body and wake up when you need to wake up, that would be great. But one of the reasons why we have such
A grogginess, it's called Sleep, inertia. When we wake up out of the wrong state, which is deep slow-wave sleep, is because I liken it to like a washing machine cycle. This 90-minute Cycles like a washing machine cycle. And and the first part is to add water, right? And then your clothes are soaking wet. You don't want to open the washing machine and try and function put them on and wear them around while they're soaking wet and full of soap. So you have to wait until the cycle is through before.
Or you can well actually, let's put it in the dryer too, before you want to wear them. So,
Yeah, you can function. It just takes a little while for those closes that brain to dry out so you can actually function well but it's better to wait through the whole cycle is complete. And so that's why you want to set that 90 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 a hundred and five hundred and ten minutes, 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 nen to REM sleep cycle which takes less time and if you wake up at it, REM sleep, there's usually no problem cognitively you care. You're good to
go. Are you a fan of sleep trackers?
Sure. Yeah. Do you use one? I have one on. I don't take I don't I don't live my life by them because they are the best ones.
Right now are about 70 percent effective at staging your sleep, so 70 percent say yes. Ok, it's ok, but take it with a grain of salt is what I'm
saying. Yeah, I've tried various ones and I compared the mattress based one to actually wear it on my ankle and stuff my wrist, but and I do find it informative, but a colleague of mine at Stanford alley. Crumb works on mindset and belief effects. Talk to me about a study. They did, where people often will bias, their sense of daytime wakefulness.
Based on their sleep score more than their subjective. Yeah score. In other words, if they were told they got a poor night's sleep, even if they got a great night's sleep in the and this was, of course, measured in the sleep lab. So they are able to compare people report, feeling more groggy and the opposite is also true that if it says 100 percent or 90 percent on your sleep score, then people will I feel great even though they might not have slept well. So this speaks to the, I don't want a placebo effect with the sort of belief effects that are woven in with a score. So it seems to me that combining subjective and objective data.
Yeah, it's probably
best and I do believe you should trust your own physiology. And the way that your body is telling you to feel because in fact, it used to be that people with insomnia weren't are 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 I I didn't sleep very well at all and that's because probably we just came out with a paper that shows that subcortical structures can be in a completely different sleep.
State than cortical structures, which is what we measure in the sleep lab, what the cortex is doing. So it might be that people who say, I did not sleep all night long, even though the cortex is saying, oh no, you had great sleep was because they're they're monitoring their subcortical hypothalamus hippocampus Thalamus. Other other structures that the sleep lab just can't access unless you have depth electrodes, which nobody really wants,
right? Because that requires
Holes in the skull then wires. Yeah. Wow. So does that mean that the last 50 plus years of sleep science? It's potentially flawed in some way because they're only recording from my guess. This would be the analogy would be. It's like recording from the surface of the ocean as opposed to the depth of the
ocean and trying to ascertain the life. Moving down deep in the depths brace
yourselves colleagues at Stanford, sleep, lab and elsewhere. But please just tell us because I think scientists want to know the
Truth. Yeah. I mean, it's not for nothing that you want to know what the cortex is doing. 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 but there is hope because in fact, it would be great. I think that's possible from the pay-per-view. 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 subcortical 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, in the cortex, has an that sleep spindle State, and, and vice versa. So, there is some hope that we can gain from people with depth electrodes or animals with depth electrodes, that we could.
Backwards machine, learn what the cortex might be able to tell us about subcortical structures from the cortical EG so
interesting. This is going to be a stimulant. Yes, stay tuned. As you can be a stimulus for development of new technology which is always going to assist in scientific discovery. There is one more thing I wanted to ask about the architecture of the night sleep in terms of early part of the night earlier, you mentioned the washout.
Out of debris and the so-called glymphatic system I think is what you're referring to. Could you tell us a little bit more about the wash out that occurs in the brain during sleep? What what that is and what roles it's thought to serve and perhaps, if there are any ways to ensure that it happens or to ensure that it doesn't happen. And obviously, we want this to
happen. Yeah. All right, great question. We talked about the circadian clock and how certain things happen at certain times. Well, one of the things that happens when we're awake and talking
Into each other is that there's a lot of plasticity that has 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 it unfolds. This process actually uses a lot of ATP. The power structure, the fuel of the brain, and it unfolds also proteins, while we're doing this, while we're using them.
Them. And so during that first part of the night, when we first fall asleep in the first 20 minutes or so we're building that adenosine back into ATP and that's probably why power naps are called Power knots because we're actually rebuilding the power. And then we're also cleaning out through the Deep slow waves of celeb sleep cleaning out all those misfolded proteins, unfolded proteins, and other things that get broken down.
Down. And, 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 slow asleep goes away.
So so what happens when a neuron is firing, is that it expands the membrane expands a little bit becomes more translucent? That's how we know one of the ways. We know that neurons expand when they fire. And so, every action potential the membrane expands a little bit, as sodium brings water into the cell and then when they're silent, they contract and so, enduring, slow, waves, that 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 mean, in terms of cleaning up, debris and transferring it to where it needs to go. So so I think of it, actually, as a bilge pump cleaning out our brain.
Interesting, I've heard about
Emphatic system in them phatak washout. I've never thought about the mechanical aspects of it before I always thought that for some reason. That now it's obvious to me that there had to be something mechanical but only now that you've educated me about this. 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 contraction of the neurons in unison and pushing the fluid through cleaning out any misfolded proteins or debris, that might occur. Yeah, on the base.
Of these metabolic pathways. And the consequence of that is to to what to leave the brain in a state of more pristine action for for the next day. Yes. That right?
Yeah, you think of it again? Like a party and if you don't clean up after that party, you try and hold another one. The next day, it's going to get more clogged, you know, it's people have a harder time moving around and enjoying themselves and if that builds up day after day, you know, it's going to be cognition. That would be the
Partygoers. Moving around, becomes hard. Yeah.
And so this bilge pump that you described as associated with the big slow waves of Deep Well of slow-wave sleep. Yeah. So this is going to occur more or less in the first third of the night. Yes that right. That's right. And are there things that inhibit this process and are there things that facilitate this process?
Yeah so well one thing to the habitat,
It's not to get it
but right and here to uh sorry to interrupt but in and is this similar to the case with growth hormone where if you go to sleep later than you would normally you miss the washout. Yeah, you've got it's not you don't delay it, you missed, you
missed the washout, right? That's right. So if you go to sleep at 1:00 or 2:00 in the morning, your sleep is still going to be dominated by N2 and REM sleep, not by slow-wave sleep. So you need to, you need to get that first bit of
sleep, would a caveats it
Be if somebody normally goes to sleep at 1:00 or 2:00 a.m. and wakes up at 10 a.m. that, if that's their normal sleep cycle. Yeah,
that should be okay. It should be. Okay, 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 releases later in the quarter cost Rune rise, that happens normally in the morning also happens later so, if everything shifted
good. Okay, yeah.
There are a few studies. I've come across that really do argue for the fact that waking up circus Sunrise. That doesn't mean at Sunrise, but within an hour or two, maybe three hours of sunrise, and going to sleep within four hours after sunset or so, these is actually better for the health of all human beings than is being a night owl. And the night owl, there's almost like a night owl Posse out there especially on social media. They get very upset.
When you say that, you should see morning sunlight that after 10, a.m. you kind of missed the boat and they get very upset because I think there are about twenty, or thirty percent of people perhaps who, who really feel like they function better staying up late and waking up late and they function much less well waking up early and going to bed early. But the data on health metrics suggest that sorry night owls that they are
wrong. Yeah. Sorry me because I'm a night
owl boy. Okay well then I'm apologizing directing and here, I am not a
The early morning person. I'm kind of more typical if I wake up, naturally around 6:30 somewhere between 6:30 and 7:30 a.m. go to sleep somewhere between 10 and 11 p.m. these are averages. But I do notice that when I force myself to get up a little earlier and go to sleep a little earlier that my mood and alertness and just overall productivity is much higher than there. Could be other
variables that are to, right? I'm a night owl. I love staying up late at
Doing we know writing, grants writing papers, watching movies, whatever it is, I love it, but I like you and like every human being on Earth had do better if I go to bed earlier and wake up earlier. So one good thing for night owls is to have a child because they will wake you up their circadian. Rhythms are so strong, they will wake up. And even if you deprive them of sleep, in the first half of the night, they will still wake up like clockwork because their circadian
And rhythms are so strong at 6 a.m. 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 just sleep deprived them and made them miss a window and made them cranky the next day and made your life more miserable. So go to bed soon. After your kids, go to bed and wake up with them. That's the way to do it. Great, the child,
alarm clock. Another reason have children. Yes, 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 Roz, you know, 5:30 a.m. every morning. But I ended up getting a bulldog. That would literally sleep 16 hours if he could a nuclear bomb, could go off and he wouldn't wake up. But, what I started to learn was that Bulldogs actually have sleep apnea there. It's a as far as I know, they're the only species that has a genetically. They're essentially an inbred sleep defect. And so I actually don't encourage people to get Bulldogs because it's kind of a cruel breed. They suffer a lot in that body that
They're born into anyway, a dog can accomplish some some of this but get the get the breed of dog that is going to wake up early. So in other words, don't get a bulldog
euromaster. Well, you know, interestingly, all all predatory animals, like, dogs and cats, and lions, and us, well more dogs. Cats and lions, then us will can sleep, you know, 16 hours a day. Ferrets are predatory. They
can create a pet ferret. Yeah, I strove and sadly also.
To work on ferrets published a number of papers delightful
animals. Yeah and great because you can study development. It's really cool 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, yeah, maybe we're not as Predator as much Predators as we think. Because, in fact, we are sleep, is somewhere between the prey and the
Predators in terms of the amount of sleep that we usually need a night. But those Predators can sleep 16 hours napping all day long and more crepuscular, perhaps like their prey are more. So, Dawn. And dusk - yeah, Dawn and dusk active. Yeah. But anyway, yes, children and dogs actually in, 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
To the bathroom. Number three is children because, you know, your when your children are young but that only lasts a few years of, they'll wake you up when they're babies. But the number one thing is pets and pets. Need to go out or cats wanting to curl up with you or whatever it is Pets. Needs, will wake you up more in the middle of the night than anything
else? Another reason to not get a nocturnal pet, people who get hamsters pretty quickly realized that they are nocturnal. They want to run on their wheel
around
Them in the living room away from where you sleep,
I vote fish tank folks. Freshwater fish tank that all sorts of reasons to not get us all working freshwater fish, tank or a child. I appreciate that vote. And I appreciate you, mentioning ferrets. And by the way, folks they are carnivores, they are not rodents. And they are, they have very elaborate brain structures and they're very smart in the same family as the honey badgers in the other muscle. It's anyway, well I shouldn't geek out too much on the mustelids or else, I'll take
The the remainder of all our time.
I'd love for you to tell us about REM sleep in the Sleep later in the night as it relates to dreams and emotionality. And this is probably the appropriate time for you to introduce us to this incredible structure in the brain, which is the locus coeruleus. It difficult structure to spell, but a beautiful beautifully named structure. I find Locust release to be just fascinating. And I know I, you know, a small fraction of what it does and I'm hoping you're going to
Kate 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.
Yeah, I'm so glad you brought this up because I can totally geek out on the locus. Coeruleus used to Locus meaning spot or place and through listening blue. So you could just count the blue spot. That's the easiest. Every animal with a brain has ably spot. And yeah, and I mean, everyone was a brain because of course,
There are animals with nervous systems that are not centralized like jellyfish, but anyway, we're digressing there. So the locus coeruleus is filled with neurons that have in them norepinephrine which is the brains version of epinephrine or adrenaline is also called noradrenaline. And what it does, is it just like, adrenaline in the rest of our bodies, it helps Primus to respond to our environment. So when Locus coeruleus neurons Fire and Fire
in a burst, we can switch our attention and they will fire in a burst. If, for example, a loud noise happens in the middle of your concentrating on something. So you can, it helps it fires and it helps you switch your attention to that thing and then learn quickly from it. So, it's really important in a stress response. It helps us do a quick one, trial learning and, and then tonic activity during the day, when you're just, you know, doing your normal going about your normal concentration, kind of activity activity,
He's is really good for sustained. Attention. It works with the cholinergic system of our basal forebrain which is really important for learning and memory also to help us learn about things and put things together but just Tonica levels are signature of wakefulness and alertness so too much is panic with a Locus realist. Activity a burst is switching attention and then tonic levels are
Are sustained constant attention. And then when we go to sleep, the locus coeruleus, slows and goes from about, on average, to hurts to, about one Hertz, 1 cycle per second, tonically. And then when we go into REM sleep, it's the only time when it shuts off completely, and it appears that that complete silence is really, really important for a number of things. And the main thing that I think it's important for is
The ability to erase and breakdown synapses that are no longer working for us. So they encode things that are false now or they are encoding things that we learned in the novelty and coding pathway instead of our of our brain that have now been Consolidated, other Pathways. And so we need to Now erase them from the novelty and coding pathway. And that is really, really important for being able to continue to learn things all of our lives. So, like erasing, that ran
Room or that, I don't know. What do you call those disks that you stick into computers
battle? Hard drive? No, thumb
drives. Yeah, you're raising your thumb drives. 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 Locust realist 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 weakened synapses. That are also really important part for Life. Important. Part of lifelong learning. Yeah, so much more, I could say about
that. Yeah, Locus. Coeruleus sounds fascinating. So it's connected to the basal forebrain. Cholinergic system the neurons in Locus coeruleus, if I'm not mistaken release.
Norepinephrine, perhaps epinephrine as
well. Well, no, the brains version of epinephrine is norepinephrine. The other thing. It also the precursor to norepinephrine is dopamine and so the source of dopamine in the hippocampus seems to be the locus URLs. And it's still a mystery is under what conditions? The look, Israel's also releases dopamine, but it's really important when we're learning something new to also, release, dopamine, or to at least Act.
Date The dopaminergic receptors in our hippocampus. So yeah. So dopamine norepinephrine and then there's also a gallon in which is important for releasing when we're stressed and it helps also without rapid learning, it works in concert with norepinephrine and in doing what it needs to do to strengthen synapses. So that we learn really quickly.
I love that there are multiple molecules involved because that signals
To a principle which is that even if people can't remember all the names that rarely and biology is something handled by just one molecule or pathway that redundancy is the rule because signaling attention to specific events is so important so that I'm going to use that as a just so story. I always say, you know, I wasn't consulted at the design phase but it makes sense to me as to why redundancy would exist in the
system. And in fact, when we form hypotheses about the brain,
We're always wrong. And the reason why we're always wrong is because it's more complicated than we like to think. And because in our brains when were forming hypotheses, it's we failed to account for all of the factors that are involved in the Galea, the neuropeptides the neurotransmitters, the physical structure of synapses. And so, when I was going through grad school, 35 years ago, we the Dogma was that every neuron contains one neurotransmitter and releases, one neurotransmitter and you had it.
Editorial neurotransmitters and inhibitory neurotransmitters, and neuromodulatory neurotransmitters, but that's as complicated as got. And then we found started talking about neuropeptides and people said, oh no, please don't don't complicate. And then we started talking about how neurons contain both neuropeptides and neurotransmitters and maybe more than one neurotransmitter,
even hormones to hormones and O Lord, you know?
It's just so complicated, but you 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. If the way I have otha sized it with it, you know, we actually need redundancy. We need all these systems to work together.
It's a, it's a daunting sometimes, but it also ensures many many careers in science and Neuroscience in particular. So note that aspiring scientist. There's plenty of room for Discovery.
Do you want me to talk about norepinephrine?
Yeah, so whatever. Yes. Well what I'd look would have loved for you to tell us about is, you know,
What role this lack of norepinephrine released during rapid eye movement, sleep is thought to achieve and maybe you could also review some of your work describing conditions under which norepinephrine invades. Yeah, and basically rapid eye movement sleep in other patterns of sleep and how that can be
detrimental. Yeah. So a lot of this is hypothetical but based on a lot of good evidence that were sewing together into a schema from which these hypotheses comes. I'll model
Kima from which the ice hypotheses come. But one thing that happens to people with post-traumatic stress disorder is that there is a lot of evidence that the Locust realist doesn't, stop firing in REM sleep. So, whereas their levels of norepinephrine might be similar to people without PTSD during the day and even during the first part of the night during the wee hours of the morning and when you measure norepinephrine levels from metabolites in the blood or the
63 with spinal fluid. You see that people with PTSD, it's during that 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 Locust rails is not shutting down during REM sleep, like, it should other evidence is heart rate. Variability when our Locus realist is firing. Our heart rates are generally a little higher and they don't vary as much as they do when the Locust.
Ellis 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 are North nephron levels are lower during REM sleep that goes away. Entirely in our heart rate is is dominated by parasympathetic rather than sympathetic activity. And also what our brain is driving, you know what are dreaming about, for example for dreaming, we're running our heart rates will go up but
Efrain levels, still should be low or off. So people with PTSD that noradrenergic, we're studying these and rats to. Is it true that our Locus tells doesn't shut off when we have post-traumatic stress disorder and the preliminary evidence is yes, it's true that it doesn't shut off. So what that would do is norepinephrine would act at synapses to prevent that weakening that you really need, for example, of novelty and coding structures.
Oh, and it keeps memories in that novelty and coding structure even once its Consolidated to the rest of the brain. So in the hippocampus, which is important for remembering things throughout our lives and it's that thumb drive. We, we need it to be erased so that we can learn new things. Once it's been Consolidated to the hard drive of our cortex and is so if we're not able to do that, we fill up
That Ram really quickly or that thumb drive really quickly, and we're not able to learn new things. So, for example, after a trauma, I talked to all the local surrealist 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 to look as realistic calm down and during REM sleep. You wanted to stop, because then, when you Consolidated that traumatic memory to the cortex, you need to erase it from the novelty and coding structures, for example, in the hippocampus.
Oh, so that then, when you're in the context of safety, you can learn those new things, those new context, and, 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 respond as you would to an early, a
Trauma, which is with beating heart and all of that. So even memories that are years past. If you're never able to downscale that novelty encoding structure and your Purge that from that traumatic memory. It will stay fresh and new and then become
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Huberman to get 20% off any of inside trackers plans. Again, that's inside tracker.com huberman to get 20% off, what approaches are you aware of that can turn down the output of locus coeruleus during these phases of sleep. And for that matter, what things can cause ramping up of locus coeruleus, during this phase of sleep, we've had a couple podcast episode so episodes and with guests talking about trauma, we had dr. Paul Conti, who's a
Stanford train, Harvard, trained psychiatrist, who talked a lot about trauma, wrote an excellent book on trauma, and certainly sleep, was emphasized as a key thing, like, get enough sleep. I hear you're saying, even if somebody would trauma gets enough, sleep, if Locus coeruleus is hyperactive during sleep, those traumas are going to persist in most of the trauma treatments, that I'm aware of our everything ranging from cognitive behavioral therapy. Talk therapy, drug therapy, EMDR hypnosis nowadays. There's a lot of interest and attention on.
Clinical studies on exploring psychedelics, high dose, psilocybin and MDMA. So that's a vast landscape. None of, which as far as I know, is really focused on sleep.
Specifically, they're not. And they should be because actually, psychedelics is a sleep-like state, and it's a REM sleep like State. Although, of course, there are some major differences. So, yeah, so much to talk about here. So, antidepressants are often noradrenergic.
Serotonergic reuptake Inhibitors. So they leave norepinephrine actually out there in the synapses. And what that does is, it inhibits, REM sleep. And if you're able to get REM sleep, it would probably be REM sleep with some noradrenergic activity. So, actually, I think. Anyway, I'm not a physician that antidepressants are counterindicated. 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
Type of adaptive REM sleep. That you really need in order to resolve those emotions and move on.
Is that statement specific to antidepressants that tickle the nor adrenergic pathway. So the one that comes to mind is I'm grouper Arbor can never pronounce a group of Prior on, which is what I think. Brand name is Wellbutrin. It's a dopaminergic and nor adrenergic Agonist sort of that's the net effect as opposed to the Prozac Zoloft variety which are ssris.
Yes. Yes but as
Our eyes themselves also are problematic. Because we didn't talk about it yet, but the dorsal raphe nucleus, which produces serotonin, which the specifics serotonin, specific serotonin reuptake, Inhibitors, block from being re-up, taken leaves too much serotonin out there. And what serotonin also is another neurogenetic ice or another neurotransmitter that's down regulated during REM sleep, that's specifically off during REM sleep. And what serotonin does is it weights
It's all of our cognition to being able to recognize novelty again. So, it sort of Weights are brain away from a sense of familiarity and toward novelty. And it might be one reason why it's an effective antidepressant, because it makes the world feel fresh and new again, right? But you, when you have a too much, you're holding a novel traumatic.
A in your novelty and coding structure to strongly already, you don't want to again wait things toward novelty, you need that absence of Serotonin also to help you get that sense of familiarity and to start erasing the novelty and coding structures. So you need both to be
absent. It's really interesting. We hear a lot about serotonin and it's not often discussed in terms of its features related to novelty enough I think and what you just
Describe accuse me to something that dr. Paul conti and others have said in terms of trauma and here, I'm paraphrasing. So my apologies to them for not getting this exactly right. That that an effective treatment for trauma does not erase the traumatic memory, but it causes a transition of what once was disturbing and invasive and maladaptive to eventually just become kind of a boring old story that has kind of a fuzzy texture to it, as opposed
This kind of sharp high-friction texture that invades our thinking and obviously are sleeping States as well. So again, and I appreciate the disclaimer the caveats around, you know, not being a clinician etcetera, but I do think that there's a lot of interest now in whether or not antidepressants are effective for trauma or not. I think these these aspects of neuromodulation as they relate to, let's call it a racing traumas, or changing the emotional load of traumas during sleep is something
Important to take note and we also have a lot of clinicians that listen to this podcast. So they should also take note please. So if I want to reduce the amount of norepinephrine released from Locus coeruleus during rapid eye movement, sleep to eliminate the troubling or maybe even traumatic memories and allow late stages of sleep each night to have their maximum positive effect. Is there anything that I can do besides avoiding
Avoiding traumas avoiding serotonergic or noradrenergic
compounds. Well I would also avoid anything just prior to going to sleep that might excite those systems. So a lot of novelty, a lot of you know, exciting stress-inducing video games try and enter sleep with as much calm as you can. So maybe deep breathing exercises, that's a beautiful way to calm your
thetic fight or flight system is deep breathing and we haven't been able to test this with rats because we can't ask them to do a deep breathing exercise. There might be a way we can do that but I haven't found out. I figured it out yet, but if there's a way you can make your sympathetic system nervous system, calm down before you go to sleep. My free for you meditation or deep breathing? Exercises might be for some a warm bath or comforting book. Nothing too exciting.
But also nothing too boring. Perhaps just something right in the middle, which makes you feel happy and calm, as what you should do. And if you instead go to sleep, while you're anxious or you're hyped up, then your sleep could become maladaptive. Another thing that happens in rats that we have yet to know. If it happens in women is that female rats have three phases of their estrous cycle.
That their Locust realist 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 estrous cycle, the locus coeruleus shuts down, just like it does in male rats, but in the other three phases, it doesn't. So, one thing that might work, and in fact, there are a few studies that show it, it could work really well is giving women after a trauma event.
Something that contains estrogen because estrogen somehow is protective against PTSD. And they know that through your retrospective studies where they gave women in emergency room, either a pill with estrogen and without and those that had Hill with estrogen in it were much less likely to get PTSD from that. Trauma has measured a year later than those that had the pill without so there are some really good Studies by Bronwyn Graham, she's out of Australia too.
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 to stas Turon also can be protective because it gets converted to estrogen. But there's something about estrogen, that's really helpful and protective about 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 we are looking into actively right now, but it's really important.
The other thing about women is that we are two to four times more susceptible to anxiety related mental health disorders, including post-traumatic stress disorder. So, if we could figure out what's happening to the locus Heroes during sleep, and women, that and then figure out a way to normalize that. So, the Locust realist is silent when it needs to be silent. I think we could go a long way in helping women be more resilient to stress related things disorders.
What are some?
Other sex differences as they relate to
sleep. Yeah, yeah, that's a really good question. There have been very few studies, unfortunately of women and sleep women and estrous cycle, or menstrual cycle and sleep. And but what we have found, which actually largely replicated this study in 1960, is that that women or females rather at high estrogen High hormonal face?
Is of their estrous cycle or menstrual cycle, sleep. A lot less, but that sleep is more efficient. So that sleep is more dense in the 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 5 to 10 Hertz in the hippocampus important for one year learning and also important. During REM sleep is also bigger and juicier
during the high hormonal phases. So even though there's less sleep, it's more efficient and better. But so, so all of that efficiency seems to be reduced in those other hormonal phases. So even though you might sleep a little more, you might need more sleep. In fact, in order to accomplish the same thing that you can get with that short, very efficient sleep of hi
My
face has very interesting. I think there is a growing Trend at least among NIH funded grants to require that as they refer to it in the grants of biological sex as a variable. And then here, we're talking about sex the verb. Although I'm sure their studies about that too. But biological sex is a variable because there is a dearth of studies exploring sex differences in in most everything there's all sorts of reasons for that. But more importantly the
The fortunately the trend is Shifting. Yeah.
And even when you study males versus females, a lot of people just say include females and their studies. But then don't track the estrous cycle or menstrual cycle and hormones have huge effects on our Behavior. I mean, just think about what you said sex, you know, before our hormones come in, we're not interested in it. And suddenly, you know, that's kind of a main driver of behaviors. Hormones can definitely change.
We are and what we do. So we should be studying hormones. Not just
sex, I always say that puberty is. Perhaps the most massive transformation and rate of Aging that any of us go through. In a short amount of time, an individual, their cognition changes, their world view changes, and that's largely, hormonal driven. And and obviously, neural architecture, has changed to. I'm very happy that you mentioned. I'm trying to get into Commerce States, prior to sleep and some ways to do that. I'm a big fan and I've talked a lot before on this podcast about
Things like Yoga Nidra, which is a non-movement based practice, sometimes called non sleep deep rest where people actually take some time each day to practice how to go into a more parasympathetic. A relaxed State deliberately because it's a bit of a skill. Yeah. It's and there's there's some good data really mostly out of a laboratory in Scandinavia showing huge increases in Nigro. Striatal dopamine when people go basically engage in a practice of deliberate non-movement.
And that the brain actually enters states of a very shallow sleep. So sort of nap ish but the idea is to actually stay awake but motionless and it does seem to restore a certain number of features of neurochemistry but perhaps more importantly, it teaches people to relax which is something that most people are not very good at but in any event and people who listen this podcast have heard me say this over and over again. So I sound like a broken record but this practice as a zero cost practice that doesn't require any.
She does seem to really enhance people's ability to fall asleep, more quickly and to fall back asleep if they wake up in the middle of the night. So in any event another plug for NST R Yoga Nidra.
Well I just also want to add to that. That's one of the reasons why insomnia is so Insidious. Is because when people feel like they haven't gotten enough sleep and they're not getting enough sleep and become anxious about getting enough sleep, and then you're anxious before going just leave like I'm not going to fall asleep, it's going to be 45 minutes in and then that's a positive feedback loop. So you need to break that Loop.
Say okay, my body's going to get as much sleep as it needs. I needn't worry about it and then practice this relaxation to say, hey it's it's all okay, it's going to be all right? And and then concentrate on things that relax, you whether it's concentrating, are not concentrating, whatever it is, you mentioned, Yoga Nidra. And that reminded me of Transcendental Meditation, which is something that also hasn't been studied, well,
Largely because we can't ask non-human animals to do it and so we don't know what's happening with our neurochemistry and our brain activity, it in a deep and meaningful way. But one thing that his has been shown in those who can do it really. Well, is that that Theta activity? That I said happens when you're learning something, or when you're in REM sleep, it's well-established and increases. During the Transcendental Meditation,
So, it might be that some states of meditation could in some ways replace or mimic some functions of, for example, REM sleep. But again, we don't know if all the neurochemistry is right to do. For example, the thing that I was talking about which is erasing the novelty encoding structures of the brain that needs an absence of norepinephrine and serotonin which we don't know. That goes away with Transcendental Meditation we just don't know the answer to that
yet. Yeah. There's
Studies on, on Yoga, Nidra and sleep replacement are kind of interesting. It does seem to be the case that nothing can really replace sleep except sleep. But that if one is sleep deprived, or is having trouble falling back asleep, that these things. Like, and I hear, it's, I acknowledge this is essentially like, Yoga Nidra, but we now call it non sleep deep breast or NST R, because often times for names, like Yoga Nidra act, as a kind of a barrier for what would otherwise be people willing to try a practice? It sounds
God. It sounds like flying carpets and Lube, you know it sounds like you have to go to Iceland by the way SL ends with a beautiful place but it sounds like you have to go there or live in the west coast to believe in this stuff, but it's simply not the case. These are practices that that are really just self-directed relaxation as a practice that that allows people to get better and better at directing their brain States towards more relaxation and most people have an asymmetry. Like, for instance, most people can force themselves to stay up later but they have a hard
I'm going to sleep earlier and that just speaks to the asymmetry. That's probably adaptive and survival base that we can ramp ourselves up far more easily than we can tend to calm ourselves
down. And actually, you know, to appeal to other Christians, like me prayer can be a wonderful way to calm yourself down because through prayer, you're giving your cares to God and saying, you know, and then you are relaxed more relaxed. And I just want to say that because
The same reason that yoga might put some people off it might put some people off to to talk about prayer but it's the same process of being able to relax and yeah
and get outside our own experience a little
bit. Yeah back out get a worldview that might actually also help us to relax.
Well, you might be surprised at how many clinicians and scientists who've come on this podcast. Have mentioned things like prayer from
Various perspective, Christianity, Judaism, Muslim, traditions, and others that as a parallel, to all of these things and I think what it speaks to is the fact that ultimately, the biological architecture is that we're all contending with are going to be identical, right? And so different ways to tap into them and ones that are congruent with people's beliefs, I think is are great
because anything non congruent with your beliefs is also
stressful and feels force. And that's why, you know, this idea of calling it non sleep deep breath.
In addition to Yoga, Nidra was not to detract from the naming or the history around Yoga Nidra, but I was finding that it was a barrier, you know, likewise Yoga Nidra tends to include things like, intentions, whereas NSD our scripts. And by the way, we will provide links to some NST R in Yoga Nidra scripts. But NS TR has no intentions is simply a body scan deep relaxation base. So it sort of the scientific version of all of this stuff and actually we study it in the laboratory and and some of the brain states that people go into. But that's a discussion for another
time.
My mother used to tell me when I said we could play. I can't go to sleep. She'd say well you know, start with your toes and relax so you would clench your muscles around your toes and relax them and do that all the way from your toes, all the way to your head and I don't know where she got this. It might have been her own common sense or she might have gotten it from this npnp our shows called the mind can keep you. Well she leased to listen to but that's another intentional relaxation that focuses on the body.
Rather than on your own mental processes. But
the, I do a little bit of work with the military, and there's a method within certain communities of Special Operations in the US military where if they can't sleep or they're having challenges sleeping, they will deliberately try and relax. Their facial muscles in particular like sort of drape, the facial muscles and use long or exhale emphasized breathing does seem to increase the probability of transitioning back into sleep.
Those are Hallmarks of Yoga, Nidra, non-slip, deep rest, body scans. And and so I think all of these things Converge on on a common theme. You know as neurobiologist we can say all of the things that we are describing certainly move the needle away from Locus coeruleus activation and we haven't done that the experiment to really look at that. But it seems all these things are counter to noradrenaline
release. Another one, is yawning, yawning and itself is with that kind of, sort of tensing of all the muscles.
Face and then relaxing them. So I might be why we on. We don't know why young yet but it might also have would be really great actually animals Ian to, you know,
my Bulldog was a Perpetual you if he wasn't sleeping, he was yawning
and it would be interesting to see what yawning does to the locus coeruleus does. That also come and switch Locus trellis activity because it's an interesting that facial nerve like trigeminal nerve, you know, the through the vagus connects in directly to the
Casillas and has a powerful effect on that
interesting. A common. I think friend of ours and direct colleague viewers Jack Feldman was a guest on this podcast telling us about all the amazing structures he and others have discovered in the in respiration and breathing, sounds like we have a collaboration Brewing. Three of us should should definitely carry out. I'd love for you to share with us a little bit more about the spindles that have come up a few time. And I don't know if it's relevant to this so if it's not, let's separate it out but I'd love for you to tell us a little
Bit about the role of sleep in problem solving, and creativity. And of, spindles are involved. And I'll consider myself lucky for batching them in the same question. And if they're not involved, simply feel free to separate them
out. I think they could be involved in. And the reason why I think that could be involved as we now know a lot more about spindles. First of all, the first thing that we knew, first of all, we ignored them. Then we thought they had something to do with keeping us asleep and that was their function is when the an external stimulus came, they would keep us asleep because they would arise. But now we know that the density
e of our sleep. Spindles, the number that we produce per minute is, well, correlated with our intelligence in the first place and that no matter what your intelligence is, and no matter what your sleep spindle density is, if you learned something during the day and increase your sleep spindle density, it's really almost perfectly correlated with our ability to consolidate that information in an incorporated, into the schema that we already have in our brain. So if you try and learn something new, even if your sleep spindle density at Baseline is great.
If you don't increase your sleep, spindles that night, you're not going to, you know, use sleep to really incorporate it. Interestingly, sleep, spindles are poor in those with schizophrenia. It's one of the characteristic signatures of sleep is that sleep spindles are very few and far between which might mean that that people with schizophrenia might not be able to incorporate new information into already existing schema. And instead, it sort of Flaps in the breeze out there and can be accessed.
Assess erroneously at times when you, you know, you don't want it to be involved. So I digress. So sleep, spindles and creativity. So one of the things we now know through some great Studies by Julie seat and Anita luthi is that sleep, spindles are accompanied by an incredible plasticity out in the distal dendrites, the listening branches of our neurons that listen to other cortical areas. So there are proximal dendrites in our neurons.
That listen to the external world and are conducted through the thalamus and then there are distal dendrites which listen to an internal kind of you know conversation that's having happening in our brains. It's kind of, you know, our internal State really and during sleep, spindles that's when those distal dendrites are able to best learn from other cortical areas and from the hippocampus, it is during sleep. Spindles of the hippocampus in the cortex are best connected and when
Plas incredible, plasticity can happen when I talk about schema. That's a cortical cortical thing. That's when, you know, the image of Santa Claus and presence, you know, comes together, it's not through some external thing. Once we learn those things together, it's our cortex that that encodes that and brings those images back up together and that's during sleep spindles when that's happening, when that, there's big surges of calcium into those distal dendrites and where plasticity happens in,
In just huge amounts during that sleeps spindle stage of sleep which is n 2 stage. There's also some another excitatory event that comes all the way from the brain stem and projects everywhere in our cortex, which is called pgo Agent P for ponds G4, geniculate nucleus of the thalamus, which is where they were first discovered and over occipital area, which is a visual area, which is again where their first discovered. But in fact, it's now been shown that pgo a
waves, which we should generalize to p waves because they come from the ponds and go to the thalamus and then the cortex happens all over the brains and that is where glutamate, which is a major excitatory. Neurotransmitter involved in learning and plasticity is being released in big amounts. Also in those distal dendrite so p, waves and spindles work together to cause plasticity. And so our schema together which could be the origins for insight and creativity. Now, when pgo waves are p waves or
Discovered it was thought to be random because this small area that generates p waves all over the brain, you know, Jen projects all the all over the thalamus and causes p waves all over and you don't measure p waves all over the brain at the same time. In fact it's just seemed sporadic and random so that's probably p. Waves also happening even more during REM sleep rapid eye movement sleep. So that's probably that's why people think that.
REM dreams are so Random is because these p waves are random and they could generate dreams because their internal source of excitation that kind of replaces the outside world during our dream state. And so these p waves. If they are random, could could function, could be the underlying reason why REM sleep dreams are random, and it might also be why creativity and happened there. Because we're
And only activating Co activating different things in our brain that we can then sew together, but it might not be as random as we think. So, that's a caveat there.
I just learned a lot from you because I teach brainstem to medical students and talk about the ponds and the ponds, like this dense collection of all these different nuclei involved in a bunch of different things and it's close by a bunch of interesting things and it's still kind of a mysterious brain area. But when I learned about pgo waves, I thought pain
ponds geniculate occipital. Migas occipital is most commonly associated with visual cortex. I thought it was the origin of the visual component of Dreams. Probably is I'm very happy to learn that they should be called p waves because they include lots of different areas of the brain. And it makes really good sense to me why the kind of pseudo randomness of Dreams, especially these late night, and early morning later in sleep. I should say, an early morning dreams seem too,
Cobbled together from disparate experiences. I know you know you know you walk through a door and suddenly it's a completely different context and Landscape. Yes, beautiful. Yeah. I like this idea. Why but it makes intuitive sense and makes biological sense. It also gives me something to talk about to the medical students. Next quarter. When I talk about
pawns, wanna talk about wearing the ponds, it's right below the locus coeruleus, it's called the sub surrealist. Their glutamatergic is also called sld, some lateral dorsal, nucleus so,
So note to any aspiring neurobiologist there's a vast landscape of yet to be undiscovered structure and functions in the ponds. You want to work on something that is sure to reveal something novel, work on the ponds because it's in every textbook, it's clinically very important structure. Sadly gliomas can. And another cancers of the brain can. Sometimes it can often surface in the ponds but but we still know very little about it. I read a paper.
This last year or two and I think it was covered in a bit of popular press that during rapid eye movement, sleep people can solve problems or respond to external stimuli like, for instance, they would give the math problems. They'd whisper in their ear while they were in REM sleep. You know what's 2 plus 2? And we would say, even though they were paralyzed apparently, they could still move their mouth because they'd say, four or something like that or they'd say, you know, what's your name? And people could respond. And so that in REM sleep, perhaps people some elements of
Cognition are still
active, I'm glad you brought that out.
That what do you think? And I don't know, the authors of that study and and listen, If Ever I say something wrong, it's great on this podcast because someone will tell us in the YouTube comments. It's one of the great uses of YouTube comments, but I'd love to know your thoughts on that study. I mean, is that just kind of a an odd feature that or does this have meaning? Should we actually care about this
result? There's no just about it. It's really actually.
An interesting and might relate to this paper that I talked about where we, we said different areas of the brain can be in different states at the same time. So, lucid dreaming is another thing we can't ask animals to do or can't ask them if they've done it, but we can certainly ask humans to do it, and some people can do it really well. And it would be really interesting to see in those people who could lucid dream really. Well, whether they spend more or less time in this asymmetrical state, where one area the brain is in one state.
And another area of the brain isn't another and it might be that those people can respond to questions during REM sleep. Best are those that have the most asymmetry or dissimilarity or dissociation between subcortical and cortical structures or it might be that they're the ones with the most symmetry, we don't know. I do worry a little bit about lucid dreaming because people are. It's a fad, people are really excited about it. And to be able to remember one's dreams is fun often, unless they're nightmares and
But it's really interesting or to be able to direct ones dreams. If they are, nightmares is really wonderful power to have to be able to redirect a nightmare that has been repeated to something else, and then kick yourself out of that repetitive nightmare is really nice. But I worry a little bit about because we know, so little about what's actually going on in the brain. And if this lucid dreaming state is preventing us from, for example, from the Locust, realist from calming down or the serotonergic.
System from silencing, like it should and maybe what we're doing during this state is. Yeah, we're activating the learning and memory structures, but in a way, that's maladaptive in terms of the Erasure that we needs to do. So, maybe one of the reasons why most people don't remember, most of their dreams is for good reason. Your hippocampus is in a state where it's not writing new memories. In fact, it's writing out its the memories it learned during the day to the cortex and its immune from incoming new information.
So, maybe lucid dreaming is bad because you're, you're activating the hippocampus in a way that's writing new memories. And it might be really maladaptive for things like, you know, PTSD on the other hand, I mean, just argue myself right out of this. When I used to have a repeated nightmare, when I was a kid, my mother whose so wise would tell me. Well, listen, just next time, you're in that dream, you know, say hey, I'm in a dream and then change something about it.
So she and I rehearsed what the horrible dream that it was it was a big monster you know running after me and my legs were like mud and I couldn't run away and it was just terrifying and that was a dream. I would have, you know, time and time again. She said, okay, next time, what are you going to do in that monster comes after you lot. So I'm gonna run away know you. That's what you do every time and it's always the same outcome, you can't run. So let's do something different. Like, what could you do? That's different. So I came up with all. I could turn around and punch it in the nose. Yeah, that's great.
And so, the next time I had that dream, I did recognize this is that same old dream, which means that there's part of my brain. That's conscious enough to know that this that I'm in a dreaming State and then I didn't have the courage in my dream because I was still terrified to punch their or touch of the, a monster in any way. But I did have the courage to turn around and look it in the eye and say, I know that was enough. I said no. And that was enough to knock me out of that, rut of that dream, so that I never had it again. I never
Had that same dream again. And in fact, it gave me peace about dreaming because I knew that if ever there was a nightmare that was just too scary, I could probably do something to change it and knock myself out of it. So even though I don't recommend lucid dreaming on a normal day to day basis. If it's enough, that can knock you out of a rut. One thing that happens with people with PTSD is they have the same repeated horrible nightmare, which is often a reliving of the day.
Trauma that they had. So maybe lucid dreaming can be used on occasion to be a powerful tool because there's so much plasticity that happens during REM sleep to knock you out of that rut of reliving that event and and just change it, you know? And you could probably practice that during wakefulness rehearse, the event that happened that was so traumatic and then just introduced a new element like you know, now
Now, I'm safe. Now, you know, the sound that was associated with that really traumatic thing. I should now associate with something Nelson, next time, I have that dream. I'm going to change it, so that sound is. Now this new thing that is should be associated with safety and that might be enough. Maybe I hope to knock you out of that repeated Nightmare and maybe even start you on the path to recovery. Because if you can calm down about those nightmares stayed sleep, then maybe your local cyrillus, which is involved in stress. Can also
Blacks and you can do the erase your parts that need to be done.
I love it. I seem to recall a paper and I'll have to find the reference and and send it to you. We will also put in the show, no captions, that described a protocol essentially matches this idea. And I think what they had people do is either Q themselves to a particular smell or tone and wakefulness, then to try and recall a recurring nightmare. Yeah. Then during the night sleep, they have the tone
Playing in the background, which would then Q them to the wakeful state, they're still asleep mind you. But in the pseudo Lucid or Lucid State, and then try and change some variable as you're describing some either, look, the predator in the eyes or do something different. Yeah. And then in the waking State take a little bit of time to try and script out a different narrative all together and it took several nights as I recall or more but that they were able to escape this recurring,
nightmare like a week or something. Yeah, so you're familiar. Yeah beautiful.
Daddy. I loved it.
Yeah, we will put a reference to that. I need to revisit that say, which pretty recent. But I need to dive into it again because I think I didn't go as deep into it as I should
have. No. No. But the one thing that you that you won't be said many right things but one of the things you said is that they were able to Q the dreamer when they knew when they were going to REM sleep, and then they played the sound or had the odor. Now, when you're normally asleep alone in your bed, you're not going to be able to chew yourself, but it might be
That rehearsal enough before you go to sleep, is enough to, you know, help qu2 that repeated nightmare remembering what the nightmare is. And then figuring out how to cure yourself to do something different
years. I had the same, recurring nightmare over and over and over again and it was so sailing and so clear and I'm not going to share what it is because it's it's not that disturbing. It was just, I think it was the emotional load of it and just how Salient certain features were like one.
Person in was a real life person had a particular clothing on, and it's like, in that just served as this q. And I don't know if I ever did any direct work to try and deal with it, but now it almost seems silly to describe it.
Well, dreams are usually silly to describe
parties, pre-selector measure pretty violent dreams.
And your emotional system is so geared up during REM sleep which is another thing we could talk about.
Yeah, please. I would love to. Yeah, so Locus coeruleus is ideally situated.
Suppressed. So we can't release norepinephrine. We can't act out our dreams this during these very emotionally Laden, thoughts, and and storylines, during sleep is almost like starts to sound like a little bit of a built-in while sleeping trauma therapy, because most trauma therapies involve trying to get people in two states of counter to what most people think you actually want to get close to the trauma. In terms of the narrative, that's a try and suppress the emotional reactivity of it.
Or, I guess that's the motivation for ketamine, based therapies for trauma, or I've also heard in this is still perplexing to me that other waking based trauma, therapies involve, taking people the other way. Making it very cathartic, take them to the peak of the emotional response but then, allow that to finally cycle down into a more relaxed response. So please, if there's anything about Locus coeruleus and dreams and that can help people basically extinguish traumas or traumatic features to do
A real life events and we definitely want to know
about the yeah, well I think one of the things that people thought might help after a trauma like a school shooting or whatever you know, car accident is to talk about it and in but in fact that ended up being counterproductive. And I think one of the reasons why it was counterproductive is because it didn't take them back down, it brought them up and continue to reactivate the emotions of it, but then didn't, you know, emphasize the safety of fact.
It's over or help them work through how they might avoid it again in the future. To calm the sympathetic nervous system down again before they went to sleep and and and it none of these studies has sleep ever been considered. But to me, that's the key. Part is bringing down your sympathetic nervous system before you go to sleep. So that your sleep can be adaptive, your look is realest. Can shut off like it normally does, or should do and then able to erase the novelty of
It, the other thing that I just mentioned a minute ago, was that the emotional system is highly activated in REM sleep, and that's definitely true, and that might seem counterproductive in terms of, you know, the nightmares. And, and how to help REM sleep. Be a therapeutic thing rather than a, than a, in reinforcing, the emotionality of the trauma. And I think the key to that again, is the absence of norepinephrine. So even
The emotional system is in high gear without norepinephrine. You can actually divorce. Those highly activated emotions from the cognitive parts of the memory that you have just written out in that NT stage of sleep. When the sleep spindles are going. So, so you just now Consolidated, the information that you'll need to survive and to, you know, to make that
Active and now you need to divorce from that schema. And from that semantic parts of memory the emotional part because whenever you remember, something is fine, if you remember the being emotional at the time, but you don't want to bring back and so into that memory all of the same emotional systems, you don't want to bring back, you know, the heart rate changes in the sweating and all of that, you want to be able to remember all the parts of it. And even remember that you were
Sized and that you did cry and that you did have, you know, your heart was racing, but when you're talking about it years later, you don't want to have to relive all that. Otherwise, who would ever want to recall a traumatic memory. Because you're basically putting yourself through the same trauma, which is what people with PTSD have. They don't want to recall this traumatic memory because it's reliving it, like it's just happening again. So that's what we're thinking. Is that the emotional parts are now? Long are
Not able to be divorced because the norepinephrine system is not downscaled during REM sleep and so that REM sleep serves to instead reinforced. And in fact amplify the emotions because your your emotional system is up. Looks real assist. High-res owing in every night, the emotionality of those memories and with the memory
itself, you've told us a lot about Locus, coeruleus and norepinephrine from Locus coeruleus. Is there any role?
All four norepinephrine epinephrine and cortisol released from the adrenals. My understanding is that norepinephrine and epinephrine will not cross the blood-brain barrier which is probably why we have a brain-based nor adrenergic system. Yeah. Locus. Coeruleus and other and other neurons Bruce actually, that's a question. I should ask you other other sites in the brain where norepinephrine is released from, or is it just Locus coeruleus?
So there are seven. Oh, nine.
Adrenergic. Yes, there's nine different adrenergic instructions. I'm
sorry I didn't ask, but but it just occurred to me that in some cases like with Raph a, there are other sources of serotonergic Drive in the brain, but Rafi is like what it means and
that's the one that goes to the cortex and the Locust Rose is also the one that goes to the cortex. But there are other adrenergic sources some that from the brain stem that descend and help us to ignore pain. For example, when we're stressed
And needing to run away from the tiger. Right? We don't want to be thinking oh my ankle hurts you know you want to just be able to ignore it and go do what you need to do. So yeah so there are lots of other noradrenergic nuclei but the local students is the main one that projects all over the brain. They actually the only place that doesn't project is the dorsal striatum. He talked about ventral striatum and addiction, the dorsal striatum is the only place to look is Rose, doesn't project to and that's involved in procedural, learning motor learning.
Kinds of learning that take over when your hippocampus. For example, is compromised, bilateral, if you don't have good hippocampus, you can still do procedural learning and do and it's great, it's a redundant system. And so if your local stylist is not working, if you don't have it anymore, you can still do a few. If you don't have a good hippocampus, you can still do learning through this dorsal striatum structure. So, it might be for those kinds of learning functions sleep deprivation, where you never let the
Locust really stopped firing is okay because it doesn't have any receptors for norepinephrine anyway so
yeah. And what about bodily the like adrenals? Yeah, you know, I offer my people there's no such thing as adrenal burnout per se, that adrenals don't actually burn out, but some people have adrenal insufficiency syndrome. Other people have adrenals that are just chronically cranking out epinephrine norepinephrine and
And cortisol at the wrong times
in particular. Yeah, yeah. So that there's a great questions and I think the answers to them have yet to be discovered the connections between our periphery and our central nervous system. But we know that there are beautiful connections and it's untapped source of being able to manipulate our brains is to work through our bodies. And so our adrenals do great things, they constrict our blood vessels causing higher, blood pressure,
Help blood rush out. Tell the extremities that need blood in our muscles. For example, for running away from the lion or the Tiger
or whatever. Doing a grant deadline working. Yeah we're catching a train.
Yes you can try and yeah the adrenals help our hearts from faster our muscles get confused with the blood. It needs diverts blood and everything away from our parasympathetic system, which is rest on Digest.
We don't really need to digest that croissant when were running for a chain, we can do that later. So it's doing really important things. What we don't know because it doesn't cross the blood-brain barrier is how that affects the brain and whether our if we can independently activate our adrenals, when a time, when our brain thinks that we should be fine and calm and asleep how our brain detects that. Is it a feedback through your heart is racing and
Rain Stone says, what's going on. My heart is racing and then wakes us up and then our hearts were racing together with our rain racing. We just don't know the answers to these questions yet. There are some good good studies old studies but we need a lot more.
I will another another nod to the fact that there's lots of great work on going and still to do. I'd love for you to tell us about some of the work that you're doing more recently on the relationship between sleep and opiate.
Use withdrawal relapse and and craving just addiction. Generally, I get a lot of questions about people, trying to come off benzodiazepines or people's challenges with benzodiazepine and other types of addiction. Yeah. What what is the role of sleep in addiction and recovery from addiction and opiates in
particular? Yeah, this is a very young area and in fact, my laboratory has just started, I have a graduate
Student who's been in my lab for just one year. She's done amazing work already but completely groundbreaking work and what she has discovered already. We don't have the paper out yet, but we're working on it is that when animals withdraw from opiates and this has been sort of replicated in other ways. With other types of things are sleep, is Disturbed. Our sleep is terribly Disturbed and the amount of sleep disturbance predicts relapse behaviors.
And you might think, well, of course you're going to relapse if you can't sleep because of opiates, calm you down. Will the reasons why opiates calm you down? Is because the locus coeruleus again, Lou spot is covered with opiate receptors and that are normally really responsive to our endogenous opiates. And so what what happens when we were pleased? For example or laughing or whatever and Dodges opiates activate those receptors and Locus rules and calm it down and it actually
Suppresses locusts, religious activity, makes us happy and relaxed. One of the things reasons why opiates are so addictive is because it also calms us down and makes us relaxed. But the problem with exoticness opiates is that they really bite strongly bind, these receptors on our local surrealist, and if you take an exigency opiates again and again, like you're recovering from surgery. For example, take this pain medications. Is that our Locus real is struggles to do what it's supposed to do.
Which is keep us awake and learning and concentrating on things. So it will down regulate. It will internalize these receptors that are normally only occupied by endogenous opiates. And and it will do this, it will change our genes that are associated with producing these receptors. So you actually have very many fewer receptors so they look Israel's at least during wakefulness can fire and the help us to do these things like learn about our environment. And so if you long-term reduce the number of receptors out there,
Then when you withdraw the exaggerating so Pious, there's not enough of your endogenous opiates to to be able to occupy those few receptors that are there. And our local service has nothing to calm it down anymore. No pacifier. And it just fires and fires and fires and that phasic and tonic High activity. Stresses us out because it's normally associated with stress. And so any exhaustion is stressor that adds to that and also activates our local Australis.
Has nothing to calm it down again and so it just keeps firing it, disturbs our sleep, and that's why maybe sleep. Disturbance is a, an indicator of hyperactive, Locus coeruleus, and, and such a good predictor of relapse behaviors because nobody likes to live in that high stress State and they will do anything to get back to normal. So the problem with with taking these drugs
That it leaves you excited and our Ansari excited, relaxed and happy but then when you come off of it, you're worse than when they're anywhere at Baseline. You take it again, it only brings you up this far because you have fewer receptors. When you come off it, you're down even more depressed and anxious and depressed as a word I use Loosely and that's
not that's not what I certainly. Central nervous system depression, I mean sleepier less motivated,
lowered me.
Food. Yeah, I mean our Locus coeruleus is actually. It's at the anxiety, kind of depression, actually the anxiety related depression. So yeah. So we don't know yet what? And there's some good research going on right now. What could restore? Our own endogenous receptors so that our own doggedness opiates can properly calm or local cyrillus once that they've been tamped down by exogenously opiates but that would be really one way that you can access.
The sleep disturbance. So we talked about sleep and the importance of sleep in terms of learning and memory, the importance of the structure of the 90-minute cycle for all of that. So you can imagine if your sleep is disturbed by too much, Locus, coeruleus activity, the, the structure and the function of those sleep spindles and that Theta, during REM sleep, and the, and the lack of norepinephrine, all of those structures, all those functions for, for learning something new, like a new Behavior.
Or that as an evolved, the drugs becomes compromised. And so that's something that Tonya lugo's in collaboration with Pamela Kennedy at UCLA that we're looking at. How is learning and memory affected by the sleep disturbance? If they are way, we can in animals that have coming off of opiates, can we restore their sleeps to normal? So that then they are less likely to do relapse kinds of
behaviors, fascinating. And I will certainly
Have to have you back on to tell us the results of those studies? Meanwhile, I think for anyone who's trying to come off opiates, exogenous opiates, and restore these systems. What I'm hearing is that it's going to take some time, but that any and all things that people can do to buffer their healthy. Normal sleep architecture, like morning and daytime, sunlight limiting bright, light exposure, lowering the temperature at night. A number of things that we've talked about in this podcast breathing
exercises meditation, whatever it is that helps. You calm yourself first?
Beep.
Yeah right witness would facilitate not just sleep but perhaps even accelerate the recovery and and shorten this period of withdrawal which from the questions I get him from what I hear, can be absolutely
brutal. Yeah. So I can imagine, I had to take opiates for. I only took it for 3 days after giving birth to my first son, I think Second Son, one of them. And, and just, I just said, after three days this is enough, I'm just going to try tile.
All and so I weaned myself not weaned. I just did a sudden, sharp cutoff and even though I felt I didn't get the hive opiates when I was taking the Tylenol coding. When I went off at boy, it was like PMS times 100. I was so anxious and upset at little things and thankfully only lasted a few hours. But if I had taken it for a week or two weeks, who knows, if that my endogenous opiate,
Actors would have been permanently down regulated and I would have been an addict. You know, an addict, I would have been addicted. I shouldn't say an addict. There's negative connotations. It's just a very physiological state. So no judgments at all associated with it. So yeah, they're powerful powerful painkillers but can also alter your entire brain and rewire it.
Yeah, well, all the more reason why I, many others are grateful that you're doing this work to figure out ways that people can recover
More quickly and more thoroughly.
I must say you've taught us a tremendous amount in in a relatively short amount of time, about the architecture of sleep, the different phases, the relationship between sleep and dreaming, and this incredible structure. Locus coeruleus. And I'm so happy. We also got into the ponds. That just Delights me because we rarely talk about the pawns on this podcast with such an interesting structure. Sex differences that are important in creativity and problem solving and, and Trauma sleep. Spindles just such a wealth of information.
And much of it that's actionable for people. So first of all, I want to say thank you for taking the time to sit down and have this conversation that. So many people are sure to benefit from. I also want to thank you for doing the work. You do even though I'm a fellow neurobiologist, I think that it's not often that we take a step back and realize that it's really the work of hard thinking hard. Strongly motivated p is old stands for principle investigator. By the way, Pete.
Is like yourself, you graduate students and postdocs that really drive the discovery forward and that lead to these new Therapeutics Physicians are wonderful. Clinicians are absolutely wonderful but clinicians. Don't develop new treatments. They employ only implement the ones that researchers discover. So thank you for being a brain Explorer with with a focus on growing. The good in the world. I know I speak for everybody when I say, thank you so
much. Thank you so much Andrew. Thank you for being an amazing. Interviewer, you brought a lot out of me.
Me in a coherent fashion that normally I can't do it. I'm speaking in public,
I don't know about that. I've heard your lectures and their superb will direct people to some of the other ones.
Well, thank you. And I also want to put a plug in for graduate students, in general, and the key and amazing role that they play in research. I'm a pi. As you said, I used to be a graduate student and a postdoc training myself, doing all of this on the ground Hands-On experimentation. It's so hard to do. It's so hard to do, right? It's so hard to think through all of that. Now,
Pii, get to be an idea person and just say, hey, why don't you do this? And hey, you know, what do you think about that? And they, of course, intellectually contributes. So much to these these planned experiments, but they also do the really hard work. And so, I just want to say thank you graduate students. Thank you to my graduate students and all graduate students out there. Thank
you. Post on repaid. And and and listen to the major institution, Stanford UCLA and all other major institutions, pay them more, please.
We need them, and they need to have a standard of living. Not, I'm not afraid to say that despite my primary employer, pay them more. They need it, they deserve
it, they deserve it absolutely
great. Well, we will absolutely have you back again, if you if you'll be willing and meanwhile, we will direct people to where they can learn more about you and your exciting work. And once again, thanks so
much. Thank you so much.
Thank you for joining me today for my discussion about sleep, mental health, physical health, and performance with dr. Gina po. I hope you found it to be as informative.
And as actionable as I did, in fact, I'm already implementing the regularity of bedtime plus or minus half an hour in order to get that growth hormone release. And I can already see, both my sleep scores improving and my feelings of daytime, Vigor and focus and other markers of sleep Health improving as well. If you're learning from, and, or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific, zero cost way to support us. In addition, please subscribe to the podcast on both Spotify, and apple and on both Spotify and apple. You can also leave us up to a five star.
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