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

Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today my guest is Dr. Gina Poe. Dr. Gina Poe is a professor in the Department of Integrative Biology and Physiology at the University of California Los Angeles. Her laboratory and research focuses on the relationship between sleep and learning.

In particular, how specific patterns of brain activity that are present during specific phases of sleep impact our ability to learn and remember specific types of information. For instance, procedural information, that is how to perform specific cognitive or physical tasks, as well as encoding of emotional memories and discarding emotional memories. Indeed, her research focuses on how specific phases of sleep can act as its own form of trauma therapy, discarding the emotional tones of memories.

In addition, her laboratory focuses on how specific phases of sleep impact things like the release of growth hormone. Growth hormone, of course, plays critical roles in metabolism and tissue repair, including brain tissue repair, and therefore has critical roles in vitality and longevity. Today you will learn many things about the relationship between sleep, learning, emotionality, and growth hormone.

One basic but very important takeaway that you will learn about today, which was news to me, is that it is not just the duration and depth of your sleep that matter, but actually getting to sleep at relatively the same time each night, ensures that you get adequate growth hormone release in the first hours of sleep. In fact, if you require, let's say, eight hours of sleep per night, but you go to sleep two hours later than your typical bedtime on any given night,

you actually miss the window for growth hormone release. That's right. Getting growth hormone release in sleep, which is absolutely critical to our immediate and long term health, is not a prerequisite of getting sleep, even if we are getting enough sleep.

As Dr. Poe explains, there are critical brain circuits and endocrine that is hormone circuits that regulate not just the duration and depth and quality and timing of sleep, but when we place our bout of sleep, that is when we go to sleep each night. So, if you have a short term minus about a half hour or so, strongly dictates whether or not we will experience all the health promoting, including mind promoting benefits of sleep.

Today's episode covers that and a lot more in substantial detail. You will learn, for instance, how to use sleep in order to optimize learning as well as forgetting for those things that you would like to forget. So, during today's episode, Dr. Gina Poe shares critical information about not just neuroscience, but physiology and the hormone systems of the brain and body that strongly inform mental health, physical health, and performance.

So, by the end of today's episode, you will be far more informed about sleep and how it works, the different roles it performs, and you will have several new actionable steps that you can take in order to improve your mental health, physical health, and performance. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Element. Element is an electrolyte drink with everything you need and nothing you don't. That means plenty of salt, magnesium, and potassium, the so-called electrolytes, and no sugar.

Salt, magnesium, and potassium are critical to the function of all the cells in your body, in particular to the function of your nerve cells, also called neurons. In fact, in order for your neurons to function properly, all three electrolytes need to be present in the proper ratios, and we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance.

Element contains a science-backed electrolyte ratio of 1,000 milligrams, that's 1 gram of sodium, 200 milligrams of potassium, and 60 milligrams of magnesium. I typically drink element first thing in the morning when I wake up in order to hydrate my body and make sure I have enough electrolytes.

And while I do any kind of physical training and after physical training as well, especially if I've been sweating a lot, if you'd like to try element, you can go to drink element that's LMNT.com slash Huberman to claim a free element sample pack with your purchase. Again, that's drink element LMNT.com slash Huberman. And now for my discussion with Dr. Gina Poe. Dr. Gina Poe, 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. So, one would at last, more or less, and what would the biology look like? What is a perfect night sleep? Oh, yeah. That's a great question. So sleep is really different from wakefulness, and in fact, can't be replaced by any state of wakefulness that we've been able to come up with so far.

Our brain chemistry is completely different, and in the different stages of sleep, which there is non-rem and REM are the two major states of sleep, and every animal we've studied so far seems to have both of those states. Anyway, those two states are entirely different from one another, too. And even within non-rem, there are three states. Stage one, which is what you slip into when you first falling asleep, it's dosing. There's kind of an interesting rhythm that goes on in the brain.

It's kind of a fast gamma rhythm. And then there's stage two, which is a really cool state. We sort of used to ignore sleep researchers because it was a transient state between wakefulness and the deep stage three slow-wave sleep, which is the most impressively different. And then, and between that and REM sleep. So stage two, I'll talk a little bit more about. And then the deep slow-wave sleep state, which is when big slow-wave sweep through our brain,

and now we realize that it cleans our brain. One of the things that those big slow-waves do is cleans our brain, and does other really important things to restore us from a day of wakefulness. And then REM sleep, which is the most popular, because that's when we have the most active dreams. And when you wake up someone out of REM sleep, they'll almost always report having dreamed something really bizarre.

That's called REM sleep, rapid eye movement sleep. So those are the four states of sleep, of human sleep. And we cycle through them every 90 minutes or so. When we go to sleep, say 10, 10, 30, 11 o'clock, our first REM sleep period comes about 105 minutes after we fall asleep, and lasts about 20 minutes.

Actually, it comes about 95 minutes and lasts 10 or 15 minutes. And then we start over again. And we have about five of those per night for a perfect night sleep, four or five, something like that. So a perfect night sleep is seven and a half, eight hours. There was a really great study that put people in a semi-darkened room with nothing but the bed for 12 hours every day for a month.

And what people did initially is because we're in a sleep deprived nation is that they slept a lot more than usual, like 10 or 11 hours of the 12. And then they leveled off after a week or two to about eight hours and 15 minutes of sleep. So you actually can't over sleep. I mean, they had nothing else to do but sleep. And they would round off to an average eight hours and 15 minutes a night. And then they spend the rest of the time twiddling their thumbs, humming tunes. Interesting.

I want to get back to the contour of a perfect night sleep. But I'm intrigued by this idea that people can't over sleep. I'm often asked whether or not we can get too much sleep and whether or not sleeping too long. Excuse me. Can make us groggy the next day. Is there anything to that? And how does one determine how long they should sleep 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 know exactly what sleep is for. So what they need is, you know, kind of. It's, you know, murky, murky. So we do know a lot of things that sleep does now for us, but we don't know how long those things take. So how long we need to sleep is also just a big question mark. But some people don't feel rested until they've slept nine hours.

Some people don't feel rested after three or four and a half. But most people, if they consistently deprive themselves of sleep so that they're only sleeping four, 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.

Can you over sleep right? You sleep to the point where it's too much, you know, that we are growing up when I was in high school. My girlfriend's dad had this belief that no one should sleep in past six a.m. So he would wake all the there were two children in that home. He would wake up the kids in that house. Yeah, this thing against over sleeping regardless of when people went, went to sleep. And I always thought that was an interesting mentality.

Yeah, it's not terrible actually because what that will do is it'll put you make you sleep your next night to get to bed on time. So it'll build up your homeostatic need if you wake up too early. But so I don't think you can over sleep. But people who sleep a lot like people who sleep over nine hours.

It's probably indicative of some other problem because in fact if you have a lot of different conditions, it will cause you to sleep a lot more probably because what it does is it interferes with your efficiency of your sleep. So if you find yourself sleeping consistently nine hours plus every night, then you might want to consult a doctor about maybe what else it might be. It could be cancer. It could be sleep apnea.

That is 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 nine or ten hours, you know, every once in a while. You mean if they're consistently sleeping from more than nine hours.

If they feel like they needed an ordered 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 incredibly, incredibly, excuse me, vivid dreams. And I'd wake up four or five hours after having gone to sleep feeling completely rested. Something that I've never really experienced. Interesting. On a consistent basis. I wanted to do mass spec on these pills. I still have no idea what was in them whatsoever.

I wanted to do mass spec on these pills. Exactly. Some people have thought that perhaps they had GHB, Gamahydroxybutyrate, which is by the way an illegal drug. It can kill you. It's not not something you want to take. No, that's not. But anyway, if ever someone can figure out what the red pills were, I'll be very. That's really great. And this is not a red pill of the of the other sort red pill. This is just the red sleep pills.

Interesting. I mean, it could have been even a placebo effect because placebo is extremely strong. So although I don't know there was really something to these red pills. Shout out to the acupuncturists and the Eastern medicine. But to return this to this idea of the architecture of a perfect night's sleep.

So you said we fall asleep. The first 90 minutes of sleep, REM sleep, rapid eye movement sleep will arrive at about 95 minutes in. Does that mean that the rest of that 90 minutes is consumed with slow wave sleep? Yeah, non REM sleep. And what about the sleep where we are lightly asleep? And we might have a dream that has us somehow thinking about movement or that we jolt ourselves away.

That often happens early in the night. Yeah, that's the first stage stage one and stage two sleep and stage two 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 near cortex, you know, processes all our cognition.

And so it's it's these spindles that are 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 during while we're falling asleep, one of the reasons we call it falling asleep is because in stage one and stage two, our muscles are relaxing.

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 we'll jerk away. So we're often that hallucination is called hypnagogic hallucination will feel like it will include some falling aspect that will wake up out of that's really interesting to me. A long felt that sensation of almost like dropping back into my head.

So much so that if I elevate my feet just slightly and I tilt my head back just slightly in order to go to sleep, I find that fall asleep much much faster. But it does feel as if I'm going to fall like almost going to do a backward summer. So I actually really like the sensation and usually because it precedes falling deeply. Yeah, that's really interesting. Somebody has to do a study of elevated feet.

Yeah, 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've learned something new that day or have experienced a new sensory motor experience, then your early sleep dreams will incorporate that experience much more than the later sleep dreams.

Later 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 Siddhartha Rubeiro, who studied the consolidation of memories from the cortex from the hippocampus to the cortex in a rat across the period of a full day sleep because rat sleep in the daytime. And he found that each subsequent REM sleep period moved that memory from the hippocampus to the first area that projects to it and then the second area and then the third area.

And you can see the memory moving through throughout the sleep period. Very cool. So I have to read that study. There's a number of different hormones associated with the different stages of sleep. We know that melatonin is a hormone of nighttime of nighttime 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 equally. And if you miss that first deep, slow-wave sleep period, you also miss that big bolus of growth hormone release. And you might get ultimately across the day just as much overall growth hormone release.

But endocrinologists will tell you that big boluses do different things than a little bit eaked 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 more synaptic space to encode it. How would somebody miss that first 90 minutes?

So let's say I normally go to sleep at 10 p.m. And then from 10 to 1130 would be this first phase of sleep. And that's when the big bolus of growth hormone would be released. Does that mean that if I go to sleep instead at 1130 or midnight that I missed that first phase of sleep? Why is it not the case that I get that first phase of sleep just simply starting later? It is a beautiful clock that we have in our body that knows when things should happen. And it's every cell in our body has a clock.

And all those clocks are normally synchronized. And those circadian clocks are synchronized. And so our cells are ready to respond to that growth hormone release at a particular time. And if we miss it, and it's a time in relation to the 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 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 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 about later and expect to capture that first phase of sleep.

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 bed times in addition to fairly consistent wake times. Yes, exactly. And in fact, one of the best markers of good neurological health when we get older is consistent bed times. 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 an issue, some underlying issue perhaps is being a teenager or an adolescent and undergoing a stage of development where there's a lot of bodily and bringing growth and exception to that because 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, they'll just sleep and sleep and sleep. Should we let them sleep and sleep? Okay, okay. So that's the one exception. What about us? Just like babies. Okay. 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 making it develop right. And if we deprive ourselves of sleep, we will actually also just like, like I said, we have a daily clock.

We also have a developmental clock and we can miss a developmental window if we don't let ourselves sleep extra like we need to. 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 p.m.

Are there things that I perhaps do in the preceding hours of the preceding day, like in just 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 it 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 hard disk, and which is the cortex and it's a unique time when they're connected.

So if you don't want to miss that, you don't want to miss REM sleep when it is also a part of consolidation process and schema changing process and alcohol in there, you know, before we go to sleep, we'll do that until we've metabolized alcohol and put it out of our bodies, it will affect our sleep badly. Probably fair to say no ingestion of alcohol within the four to six hours preceding sleep given the half life or 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 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 short change yourself on. And I think that's the stage.

Many studies are showing that those are the times in sleep when the most creativity can happen. That's when our dreams can incorporate and put together old and new things together into a new way. And our schema are built during that time. So yeah, we can change our minds best during those phases of sleep. Could you elaborate a little bit more on schema? No one, I don't think anyone on this podcast has ever discussed schema.

I'm a little bit familiar with schema from my courses on psychology, but it's been a while. So maybe you could just refresh mine and everyone ever. Well, it's still a concept. Sure. How do you define schema? I think of schema as like we have a schema of Christmas. Right. We have all kinds of ideas that we sow together and call Christmas a holiday season in the Northern hemisphere.

It's cold. We have Santa Claus and reindeer and jingle bells and even things that are false that, but we normally associate with Christmas presents, family gathering when it is all of this stuff is sewn together into one. There's a thread linking them all and we can just give ourselves a list of words and and none of them contain the word Christmas and then ask people later.

Give them another list of words and include the word Christmas and they'll say, oh yeah, that word was there because in their minds, they brought up that word Christmas because it's part of that whole schema. So that's what it's sort of a related lot of related concepts, I guess. I think about sort of like the desktop of my computer would scare some people, but it's just a ton of folders. Yeah.

Each of the folder names means something very clear and specific to me, right. And inside of those folders are collections of things that make sense in terms of how they're batch. Exactly. That's exactly. No, that's a great way to think of it. And when you're in REM sleep in the later parts of the night and that transition to REM, that's when your computer of your brain is opening folders and comparing documents.

Is there anything the same, these two documents look very much the same, but there's a little bit of difference and it can link those conceptually so that that's probably one of the origins of creativity is finding things that are related, maybe just linked a little bit and you can find that link and strengthen it if it. You know, make sure scheme that interesting and different.

Yeah, very interesting. Many people, including myself tend to wake up maybe once during the middle of the night to use the restroom. I've tried to drink less fluid before going to sleep. I've heard also that the impulse to urinate, forgive the topic, but a lot of people deal with this. So the impulse to urinate is also dictated by how quickly you drink fluid, not just the total volume.

I switched to sipping fluids more slowly from my last beverage of the day, which seems to help. But the point here is that I think a lot of people wake up once in the middle of the night, oftentimes to use the restroom, but sometimes just around 3 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 homeostatically regulated. And so really don't worry about how much you're sleeping as long as you're not intentionally depriving yourself of sleep by doing something really rewarding and exciting because even that is stressful to your body and describes you a lot of things we're talking about.

So don't worry about it. It's absolutely normal to wake up at least once in the middle of the night to go to the bathroom. And as long as you can get back to sleep in a reasonable amount of time, 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, going to bed a little earlier.

If I understand correctly, there's a little bit of asymmetry to sleep that catching that first phase of sleep, it's like you either get it or you don't and you have to get it by going to sleep essentially the same time. Maybe plus or minus 15 minutes or so. 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.

Yeah, yeah. And we don't know actually the answer to whether or not the sleep in the middle between that early sleep and the late sleep is in fact different for another reason and whether depriving yourself of sleep from say one to two 30 in the morning is bad in a different way. 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 incredibly vivid. I don't always remember them, but what is unique perhaps about the architecture of dreams and sleep in the let's say the last third of the night or the second half of the night. We have longer REM sleep periods and those are considered the deepest sleep even though slow wave sleep big slow waves considered deep. It is deep.

Yeah, they call slow wave sleep deep sleep and REM sleep rapid. I mean, but now you're telling me that REM sleep is actually the deeper sleep. Okay, there needs to be a new nomenclature sleep researchers. Yeah, really should go deeper. No, no, please. The reason why you call slow wave sleep deep sleep is because it's difficult to arouse people out of that state.

And when you do arouse them out of that state, they're 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 was so vivid.

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 rapid. I mean, it's more dense and often people will incorporate that sound into their dreams. So the body and brain are somehow conscious of the sound.

And I've heard also smells can even make it into our dreams and REM sleep, but that we it doesn't arouse us. It doesn't arouse us as often. Yeah. And maybe one of the reasons why REM sleep is deeper, especially in adults and older people that deep slow wave sleep goes away. So it's not as deep. It's not as big the slow waves aren't as large, which is probably problematic, but we're not sure. And so then REM sleep becomes the deepest stage.

Actually, in children, it's kind of a toss up because they it's really hard to wake them up out of that deep slow wave sleep. And in fact, fire alarms don't wake them up even really loud fire alarms out of that state of sleep.

So that's why they're trying to change fire alarms so that instead of something that the kids don't associate with anything like the root whatever they don't associate when it says their name or something else that maybe 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 you get home and the kids are asleep in the back seat. You can literally throw them over your shoulders gently, of course, and put them to sleep and it they are completely out. Yeah, it's wonderful. It is wonderful. One of nature's gifts. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens.

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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 paralyzed and that's really good because that's the time when we're actively dreaming storyline dreams and we could hurt ourselves. We're actually really cut off from the outside world in terms of, you know, responding to say this table or window or door.

And so different from sleep walking, which is out of slow asleep, out of slow asleep, that sleep walking 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 asleep. It's scary because you never know what you're going to do. You don't have voluntary voluntary control over it.

You don't have no conscious control over it, but you can actually safely navigate some situations in sleep walking 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 want 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 or talking in sleep? I don't know how many relationships have been saved by sleep talking, but I'm guessing a few have been destroyed. And I'm guessing that talking in sleep could have meaning or perhaps has no meaning just as dreams could have meaning or no meaning as we recall them.

Yeah, do not take sleep talking seriously, no matter what people say, it doesn't necessarily reflect truth. So it's not like you're being more truthful when you're sleep talking. You just saved a number of relationships. I'm not directing this at anyone in particular, but I guarantee you just did noted. So as people start to approach morning or the time when they normally would wake up, I've heard that it's important to if possible, complete one of these 90 minute cycles prior to waking up.

That is, if you set your alarm for halfway through one of these 90 minute cycles that come late in the night of sleep, that it can lead to rather groggy patterns of waking. So I'll just ask you directly, do you use an alarm clock? I do not. Thankfully, I'm in a line of work that doesn't require me normally to do anything at any particular time. I do it when I do it. Unless I have to catch a plane and then I always set my alarm just in case.

As a fellow academic, I can tell you there are plenty of punishing features about being an academic scientist that offset the fact that you don't have to use an alarm clock, but it is nice that you can often set your own schedule. So would you recommend that if possible, that people not use an alarm clock?

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 groggyness is called sleep inertia when we wake up out of the wrong state, which is deep slow wave sleep is because I like in it to like a washing machine cycle.

And the first part is to add water, right? And then your clothes are soaking wet. You don't want to open the washing machine and try and function, put them on and wear them around while the soaking wet and full of soap. So you have to wait until the cycle is through before you can well actually let's put it in the dryer to before you want to wear them. So yeah, you can function. It just takes a little while for those clothes that brain to dry out so you can actually function well.

But it's better to wait through the whole cycle is complete. And so that's why you want to set that 90 minute alarm clock. Again, that's around 90 minutes because the first stage of sleep, the first cycle of sleep is actually a little longer, more like 105 and 10 minutes, but then the second ones and third ones, they get sort of shorter and shorter is the night goes on.

And in the last few cycles, you're just doing the end to REM sleep cycle, which takes less time. And if you wake up out of REM sleep, there's usually no problem cognitively. You're good to go. Are you a fan of sleep trackers? Sure. Yeah. Do you use one? I have one on I don't take I don't live my life by them because they are the best ones right now are about 70% effective at staging your sleep. So 70% is OK. It's OK. But take it with a grain of salt is what I'm saying.

I tried various ones and I compare the mattress based one to actually wear it on my ankle instead of my wrist. But I do find it informative, but a colleague of mine at Stanford, Ali, Crumb, who 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 score.

In other words, if they were told they got a poor night sleep, even if they got a great night sleep in the and this was of course measured in the sleep lab. So they they're able to compare people report feeling more groggy. And the opposite is also true that if it says 100% or 90% on your sleep score, the people I feel great, you know, they might not have slept well. So this speaks to the I don't want to say placebo effect with the sort of belief effects that are woven in with a score.

And so it seems to me that combining subjective and objective data is probably. And I do believe that you should trust your own physiology and the way that your body is telling you to feel because in fact.

It used to be that people within Somnia weren't 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 and they say, I didn't sleep very well at all. And that's because probably we we just came out with a paper that shows that subcortical structures can be in a completely different sleep state than cortical structures, which is what we measure in the sleep lab.

And 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. 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 and 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 I guess this would be the analogy would be it's like recording from the surface of the ocean as opposed to the depth of the ocean. Right and trying to ascertain the life moving down deep enough.

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's hope because in fact, it would be great. I think that's possible from the paper if you look at it, it's in PNAS this year that you could detect subtle changes in the cortical EEG that might be able to tell you what the sort of subcortical structures are doing. Things like the absolute power in that sleep spindle band that sigma band would change if the hippocampus is in REM sleep and cortex is in that sleep spindle state 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 EEG. Interesting. This is going to be a stimulus for development of new technology, which is always going to assist in scientific discovery.

There's 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 wash out of debris and the so-called glimphatic 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 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.

Right. And obviously we want this to happen. Yeah. Yeah. All right. Great question. We talked about the circadian clock and how certain things happen at certain times. Well, one of the things that happens when we're awake and talking to each other is that there's a lot of plasticity. There's something that I'm learning from you today and you're learning from me. And that changes our synapses and it changes the way our proteins are going to be folded and changed during sleep.

It unfolds. This process actually uses a lot of ATP, the power structure, the fuel of the brain. And it unfolds also proteins while we're doing this while we're using them. And so during that first part of the night, when we first fall asleep in the first 20 minutes or so, we're building that adenosine back into ATP.

And that's probably by power naps are called power naps because we're actually rebuilding the power. And then we're also cleaning out through the deep slow waves of slow waves sleep, cleaning out all those misfolded proteins and folded proteins and other things that get broken down and.

And we don't need to be rebuilt when we're asleep because of its use during wakefulness. So I liken that to having a big party during wakefulness and you need all those party goers 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 sleep goes away.

So what happens when a neuron is firing is that it expands the membrane expands a little bit becomes more translucent. That's how we know one of the ways we know that neurons expand when they fire. And so every action potential the membrane expands a little bit as sodium brings water into the cell. And then when they're silent, they contract.

So in during slow waves, the cool thing is that the reason why you can measure them is that all the neurons at the same time, not all of them, but a good portion of them are firing at the same time and silent at the same time. And so you think about that as contracting and expanding all at the same time. It's kind of like a build pump of the brain so that can pump out.

And so that are also really important for this in terms of cleaning up debris and transferring it to where it needs to go. So so I think of it actually as a build pump. Cleaning out our brain. Interesting. I've heard about the glimphatic system and the lymphatic wash out. I've never thought about the mechanical aspects of it before. And I 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 cerebral spinal fluid just starts washing through. But here you're talking about literally an expansion and a contraction of the neurons in unison and pushing the fluid through cleaning out any misfolded proteins or debris that might occur on the basis of these metabolic pathways. And the consequence of that is to what to leave the brain in a state of more pristine action for for the next day.

Yeah, 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. And it's 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 party. Goers moving around becomes hard. And so this build pump that you describe is associated with the big slow waves of deep well slow wave sleep.

So this is going to occur more or less in the first third of the night. Is 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 inhibit it's not to get it. Right. And here to sorry to interrupt. But it and is this similar to the case with growth hormone where if you go to sleep later than you would normally you miss the wash out. Yeah, it's not you don't delay it.

You miss the wash out. That's right. That's right. So if you go to sleep at one or two in the morning, your sleep is still going to be dominated by N2 and REM sleep, not by slow wave sleep. You need to you need to get that first bit of sleep would a caveat to that be if somebody normally goes to sleep at one or two 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. Yeah, there are a few studies I've come across that really do argue for the fact that waking up, circuit sunrise.

I mean at sunrise but within an hour or two maybe three hours of sunrise and going to sleep within four hours after sunset or so. Is actually better for the health of all human beings than is being a night out and the night out 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.

And they get very upset because I think there are about 20 or 30% of people perhaps who really feel like they function better staying up late and waking up late and they function much less well waking up early and going to better but the data on health metrics suggests that sorry night owls that they are wrong. Yeah, sorry me because I'm a night owl. Oh boy, okay. Well then I'm apologize and directly and here I'm not a really early morning person.

I'm not a 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 and there could be other variables there too.

Absolutely right. I'm a night owl. I love staying up late at night doing you know writing grants writing papers watching movies whatever it is I love it.

But I like you and like every human being on earth that 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 up their circadian rhythms are so strong they will wake up and even if you deprived them of sleep in the first half of the night they will still wake up like clockwork because their circadian rhythms are so strong at 6 a.m.

and so what you 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 and other reason children. 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 because I was just having 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 a sleep apnea

there's a as far as I know they're the only species that has a genetically red 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 or a master

interestingly all all predatory animals like dogs and cats and lions and us well more dogs cats and lions than us will can sleep you know 16 hours a day ferrets are predatory they prefer it yeah I still and sadly I also used to work on ferrets publishing number of papers delightful animals yeah and great because you can study development

really cool because they're born very ultra shale like we are with brains that are not very well developed and see what happens to 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 and they're more crepuscular perhaps like their prey are more so dawn and yes yeah down and 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

helps people up at night and number two is going to the bathroom number three is children because you know you're when your children are young but that only last a few years that they'll wake you up when they're babies but the number one thing is pets and pets needing to go out or cats wanting to curl up with you or whatever it is pets needs will wake you up more in the middle of the night than anything else

but the other reason to not get a nocturnal pet people who get hamsters pretty quickly realize that they are nocturnal they want to run on their wheel around yeah you got to put them in the living room away from where you sleep I vote fish tank folks fresh water fish tank

there are all sorts of reasons to not get us all or think fresh water 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 they're very smart

yeah in the same family as the honey badgers and other mustleids anyway well I shouldn't geek out too much on the mustleids or else I'll take the remainder of all our time I'd love for you to tell us about REM sleep and the sleep later in the night as it relates to dreams and emotionality

and this is probably the appropriate time for you to introduce us to this incredible structure in the brain which is the locustsirulius a difficult structure to spell but a beautiful a beautifully named structure I find locusts 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 educate me 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 locustsirulius please do locusts meaning spot or place and surrealist meaning blue so you could just call it the blue spot that's the easiest every animal with a brain has a blue spot and yeah and I mean every animal with a brain because of course there are animals with nervous systems that are not centralized like jellyfish but anyway we're digressing there

so the locustsirulius is filled with neurons that have in them nor epinephrine which is the brain's 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 locustsirulius 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 then a tonic activity during the day when you're just you know doing normal going about your normal concentration kind of activity activities is really good for sustained attention it works with the colonergic system of our basal forebrain which is really important for learning and memory also

to help us learn about things and put things together but just tonic levels are signature of wakefulness and alertness so too much is panic with the locustsirulius activity a burst is switching attention and then tonic levels are sustained constant attention when we go to sleep the locustsirulius slows and goes from about on average two hurts two about one hurts one cycle per second tonically and then when we go into REM sleep it's the only time when it shuts off completely

and it appears that that complete silence is really really important for a number of things and the main thing that I think it's important for is the ability to erase and break down synapses that are no longer working for us so they encode things that are false now or they are encoding things that we learned in the novelty encoding pathways of our brain that have now been consolidated to other pathways and so we need to now erase them from the novelty encoding pathway

and that is really really important for being able to continue to learn things all of our lives so like erasing that RAM or that what do you call those disks that you stick into computers that are no hard drive I know thumb drives

yeah you're racing your thumb drives that thumb drives what you carry around all day long and then during sleep you write that thumb drive to the cortex to the long-term memory structures and you need to refresh that thumb drive and that's what happens during REM sleep when the locus realis is off

because whenever it's on and neurodrennel is there it helps us to put things together it helps us to learn and strengthen synapses but it does not allow us to actually weaken synapses that are also a really important part of life long learning yeah so much more I could say about that yeah locus cerulius sounds fascinating so it's connected to the basil for brain call anurgic system the neurons in locus cerulius if I'm not mistaken release North and Ephone perhaps epinephrine as well

well no the brain's version of epinephrine is North and Ephone the other thing it also the precursor to norepinephrine is dopamine and so the source of dopamine and the hippocampus seems to be the locus cerulius and it's still a mystery is under what conditions the locus cerulius also releases dopamine but it's really important when we're learning something new to also release dopamine or to at least activate the dopaminergic receptors in our hippocampus

so yeah so dopamine and orpinephrine and then there's also galleonin which is important for releasing when we're stressed and it helps also without rapid learning it works in concert with norpinephrine 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 us to a principle which is that even if people can't remember all the names that rarely in biology is something handled by just one molecular 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

absolutely 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 we're forming hypotheses it's we fail to account for all of the factors that are involved you know the glia, the neuropeptides, the neurotransmitters, the physical structure of synapses

and so when I was going through grad school 35 years ago we the dogmo was that every neuron contains one neurotransmitter and releases one neurotransmitter and you had excitatory neurotransmitters and inhibitory neurotransmitters and neuromodulatory neurotransmitters but that's as complicated as God

and then we 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 and maybe even hormones too.

And hormones and oh lord you know it's just so complicated but I mean God admit that's why it works right and every time the brain teaches us something new about itself that we didn't hypothesize we say oh of course that wouldn't work if the way I hypothesized it with it you know we actually need redundancy we need all these systems to work together. So it's daunting sometimes but it also ensures many many careers in science and neuroscience in particular.

So note that aspiring scientists there's plenty of room for discovery. Do you want me to talk about neuropenephrine? Yeah so what I'd love for you to tell us about is you know what role this lack of neuropenephrine release during rapid eye movement sleep is thought to achieve and maybe you could also review some of your work describing conditions under which neuropenephrine invades. Yeah invades sleep. Rapid eye movement sleep and other patterns of sleep and how that can be detrimental.

Yeah so a lot of this is hypothetical that based on a lot of good evidence that we're sowing together into a schema from which these hypotheses come so a model schema from which the hypotheses come but one thing that happens to people with post-traumatic stress disorder is that there is a lot of evidence that the locustarilis doesn't stop firing in REM sleep.

So whereas there are levels of neuropenephrine 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 neuropenephrine levels from metabolites in the blood or the cerebral spinal fluid you see that people with PTSD it's during the wee hours of the morning when you have the most REM sleep that they have their neuropenephrine levels differentiate most from those that don't have PTSD.

And so that's evidence that the locustarilis is not shutting down during REM sleep like it should. Other evidence is heart rate variability when our locustarilis is firing, our heart rates are generally a little higher and they don't vary as much as they do when the locustarilis is not firing. So during slow-wave sleep normally we have this big juicy variability in heart rate with every breath in and breath out because our neurodinergic levels, our neuropenephrine levels are lower.

During REM sleep that goes away entirely and our heart rate is dominated by parasympathetic rather than sympathetic activity and also what our brain is driving. You know what our dreaming about for example for dreaming we're running our heart rates will go up but neuropenephrine levels still should be low or off.

So people with PTSD that neurodinergic we're studying these in rats too is it true that our locustarilis 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 neuropenephrine would act at synapses to prevent that weakening that you really need for example of novelty encoding structures and it keeps memories in that novelty encoding structure even once it's consolidated to the rest of the brain. So in the hippocampus which is important for remembering things throughout our lives and this that thumb drive we need it to be erased so that we can learn new things once it's been consolidated to the hard drive of our cortex.

And so if we're not able to do that we fill up that ram really quickly or that thumb drive really quickly and we're not able to learn new things. So for example after trauma I talked to all the locustarilis responding in stressful situations that's great it's very adaptive but then you need it to stop once you've learned what you need to learn from it and you want to go to sleep you need the locustarilis to calm down and during REM sleep you want it to stop because then when you consolidate that traumatic memory to the cortex you need to

erase it from the novelty encoding structures for example in the hippocampus so that then when you're in the context of safety you can learn those new things those new 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 recent trauma which is with beating heart and all of that.

So even memories that are years past if you're never able to downscale that novelty encoding structure and you purge it from that traumatic memory it will stay fresh and new and then become maladactive. What approaches are you aware of that can turn down the output of locustarilis during these phases of sleep and for that matter what things can cause ramping up of locustarilis during this phase of sleep.

We've had a couple podcast episodes solo episodes and with guests talking about trauma we had Dr. Paul Conti who's a Stanford trained Harvard trained psychiatrist who talked a lot about trauma wrote an excellent book on trauma and certainly sleep was emphasized as a key thing like get enough sleep but here you're saying even if somebody with trauma gets enough sleep if locustarilis is hyperactive during sleep those traumas are going to persist in most of the trauma treatments that I'm aware of are everything ranging from cognitive behavior.

Behavioral therapy talk therapy drug therapy EMDR hypnosis nowadays there's a lot of interest in attention on clinical studies on exploring psychedelics. Hydrocybony and MDMA so that's a vast landscape. None of which as far as I know is really focused on sleep specifically. No, they're not and they should be because actually psychedelics is a sleep like state in REM sleep like state although of course there's some major differences so yeah so much to talk about here.

So antidepressants are often neurodinergic or serotonergic reuptake inhibitors so they leave neuropanephrine 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 neurodinergic activity so actually I think anyway I'm not a physician that antidepressants are counter-integated you don't want to take them if you've experienced a trauma

and you're experiencing PTSD because if anything it's going to make it worse or at least prevent the type of adaptive REM sleep that you really need in order to resolve those emotions and move on. Is that statement specific to antidepressants that tickle the neurodinergic pathway so the one that comes to mind is group of hyper can ever pronounce it group of piron which is what I think a brand name is well butrin.

It's a dopamine orgic and noradrin orgic agonist that's the net effect as opposed to the pros axol aphoride which are SSRI's. Yes yes but SSRI's themselves also are problematic because we didn't talk about it yet but the dorsal raffa new clase which produces serotonin which the specific serotonin is specific serotonin reuptake inhibitors block from being reuptaken leaves too much serotonin out there and what serotonin also is another way to get rid of the virus.

Also is another noradrin orgic and sorry another neurotransmitter that's down regulated during REM sleep that's specifically off during REM sleep and what serotonin does is it waits all of our cognition to being able to recognize novelty again so it sort of waits. Our brain away from a sense of familiarity and toward novelty and it might be one reason why it's an effective.

It's an antidepressant because it makes the world feel fresh and new again right but you when you have too much you're holding a novel traumatic memory in your novelty and coding structure too 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.

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 amcuse me to something that Dr Paul Conti and others have said in terms of trauma and here I'm paraphrasing some 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.

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 to 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 etc 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 erasing traumas or changing the emotional load of traumas during sleep is something important to take note we also have a lot of clinicians that listen to this podcast so they should also take note please so if I want to reduce the amount of norepinephrine release from locust serulius 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 certain or agonurgic compound 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 sympathetic

fight or flight system is deep breathing and we haven't been able to test this with rats because we can't ask them to do a deep breathing exercise there might be a way we can do that but I haven't found out or figured it out yet but if there's a way you can make your sympathetic system nervous system calm down before you go to sleep might free free you meditation or deep breathing exercises might be for some

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 ester cycle that their locustrials 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 ester cycle the locustrials shuts down just like it does in male rats but in the other three phases it doesn't so one thing that might work and in fact there are a few studies that show it

could work really well is giving women after a trauma event something that contains estrogen because estrogen somehow is protective against PTSD and they know that through your retrospective studies where they gave women an emergency room either a pill with estrogen or without and those that had pill with estrogen in it were much less likely to get PTSD from that trauma as measured a year later than those that had the pill without so

there's some really good studies by Bronwyn Graham she's out of Australia to really hone in on how much estrogen do you need and also testosterone just so you know gets converted to estrogen in the brain so testosterone also can be protective because it gets converted to estrogen

but there's something about estrogen that's really helpful and protective about that from from the high locustrials firing and this is again preliminary data that we don't have full we don't have all the answers yet and we are looking into it actively right now but it's really important

the other thing about women is that we are two to four times more susceptible to anxiety related mental health disorders including post-traumatic stress disorder so if we could figure out what's happening to the locustrials during sleep in women and then figure out a way to normalize that so the locustrials is silent when it needs to be silent I think we could go a long way in helping women be more resilient to stress related disorders

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 in sleep women and ester cycle or menstrual cycle in sleep and but what we have found which actually largely replicated the study in 1960

is that women or females rather at high estrogen high hormonal phases of their ester cycle or menstrual cycle sleep a lot less but that sleep is more efficient so that sleep is more dense in those sleep spindles which I haven't gone into what they might do except this connection between the hippocampus and cortex but those sleep spindles are more dense and more coherent across the brain areas

the theta cycle which is 5 to 10 hertz in the hippocampus important for one year learning and also important during REM sleep is also bigger in GCR during the high hormonal phases so even though there's less sleep it's more efficient and better

but so all of that efficiency seems to be reduced in those other hormonal phases so even though you might sleep a little more you might need more sleep in fact in order to accomplish the same thing that you can get with that short very efficient sleep of high hormonal phases 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 not him about sex the the verbal though I'm sure there are studies about that too but biological sex is a variable because there is a a lot of studies exploring sex differences in most everything there's there are all sorts of reasons for that but more importantly fortunately the trend is shifting and even when you study males versus females a lot of people just say include females in their studies but then don't track the

ester cycle and menstrual cycle and hormones have huge effects on our behavior I mean just think of it when you said sex you know before 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 who 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 of you changes and that's largely hormonal driven and obviously neural architecture is changed too I'm very happy that you mentioned I'm trying to get into calmer states prior to sleep and some ways to do that I'm a big fan and I've talked a lot

before in 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 K relax 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 niger stride will 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

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 to relax which is something that most people are not very good at but in any event and people who listen to this podcast have heard me say this over and over again so I sound like a broken record but this practice as a zero cost practice that doesn't require any form ecology 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 nsd are 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

getting enough sleep and become anxious about getting up sleep and then your anxious before going to sleep like I'm not going to fall asleep is 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 is going to get as much sleep as it needs I needn't worry about it and then practice this relaxation to say hey it's all okay it's going to be all right and and then concentrate on things that

relax you whether it's concentrating or not concentrating whatever it is you mentioned yoga nidra and that reminded me of transcendental meditation which is something that also hasn't been studied well are largely because we can't ask nonhuman animals to do it and so we don't know what's happening with our neurochemistry and our brain activity in a deep and meaningful way but one thing that

has has been shown in those 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 it's well established and 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 neuro benefit and serotonin which we don't know that goes away with with transcendental meditation we just don't know the answer to that yet the studies on on yoga nidra and sleep

placement 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 nsdr because oftentimes for names like yoga nidra act as a kind of a barrier for what would otherwise be people willing to try

to say sounds mystical it sounds like flying carpets and you know it sounds like you have to go to Esselin by the way Esselin is a beautiful place but it sounds that you have to go there or live in the west coast to to believe in this stuff but it's simply not the case these are practices that that are really just I'm 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 heart I'm going to sleep earlier and that just speaks to the asymmetry that's probably adaptive and survival based 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 caries 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 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 world view that might actually also help us to relax. Well you might be surprised at how many clinicians and scientists who 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 architectures that we're all contending with are going to be identical right and so different ways to tap into them.

And ones that are congruent with people's beliefs I think is are great. Yeah because anything non congruent with your beliefs are also stressful and feels forced and that's why you know this idea of calling it non sleep deep rest in addition to yoga needra was not to detract from the naming or the history around

the yoga needra but I was finding that it was a barrier you know likewise um yoga need your attention include things like intentions whereas NSTR scripts and by the way we will provide links to some NSTR and yoga need your scripts but NSTR has no intentions it's simply a body

scanned deep relaxation base so it's 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.

This is hard not 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 later ahead and I don't know where she got this it might have been her own common sense or she might have gotten it from this NPR show called the mind can keep you well she still listen to but that's another intentional relaxation that

focuses on the body and rather than on your own my mental processes but 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 emphasize breathing

does seem to increase the probability of transitioning back into sleep and those are hallmarks of Yoganidra non sleep deep rest body scans 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 a really as activation and we haven't done that the experiment to really look at that but 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 like muscles in your face and then relaxing them so it might be why we on we don't know why we on yet but it might also have to be really great actually animals

you know my bulldog was a perpetual if he wasn't sleeping he was yawning and it would be interesting to see what yawning does to the locus roost does that also calm and switch the locus roost activity because it's an interesting that facial nerve like trigeminal nerve you know through the Vegas connects indirectly to the locus roost and has powerful effect on that

interesting 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 yeah 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 times and I don't know if it's relevant to this so if it's not let's separate it out but I'd love for you to tell us a little bit about the role of sleep in problem solving and creativity and if spindles are involved 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 and the reason why I think that could be in focus 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 external stimulus came they would keep us asleep because they would arise but now we know that the density of our sleep spindles the number that we produce per minute is well correlated with our intelligence in the first place and that no matter what your intelligence is and no matter what your sleep spindle density is

if you learn something during the day and increase your sleep spindle density it's really almost perfectly correlated with our ability to consolidate that information and incorporate it into the schema that we already have in our brain so if you try and learn something new even if your sleep spindle density at baseline is great if you don't increase your sleep spindles that night you're not going to you know use sleep to really incorporate it

interestingly sleep spindles are poor in those with schizophrenia it's one of them characteristic signatures of sleep is that sleep spindles are very few and far between which might mean that that people with good 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 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 see and Anita Luther 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 phalamus and then there are distal dendrites which listen to an internal kind of you know conversation that's happening 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

that's when those distal dendrites are connected and when that class 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 in 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 and brings those images back up together and that's during sleep spindles when that's happening when that

is of calcium into those distal dendrites and where plasticity happens in just two amounts during that sleep spindle stage of sleep which is end to stage there's also some another excitatory event that comes all the way from the brainstem and projects everywhere in our cortex which is called p-do waves which is p for pons, g for in

that nucleus of the phalmus which is where they're first discovered and O for occipital area which is a visual area which is again where they're first discovered but in fact it's now been shown that p-do waves which we should generalize to p waves because they come from the pons and go to the phalmus and then the cortex happens all over the brains and that is where glutamate which is a major excitatory

neurotransmitter involved in learning and plasticity is being released in big amounts also in those distal dendrites so p waves and spindles work together to cause plasticity and so our schema together which could be the origins for inciting creativity now when p-do waves or p waves are first discovered it was thought to be random because this small area that generates p waves all over the brain you know, projects all over the phalmus and causes p waves all over and you

don't measure p waves all over the brain at the same time in fact it's just seems sporadic and random so that's probably and p waves also happening even more during REM sleep, rapid i-mov-ed 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 they're an 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 if they are not in the end of the brain they're not in the end of the brain

dreams are random and it might also be why creativity can happen there is because we're randomly activating co-activating different things in our brain that we can then sew together but it might not be as random as we think so that's a caveat there I just learned a lot from you because I teach brainstem to medical students and talk about the pons and the pons is like this dense collection of all these different nuclei involved in a bunch of different things

and it's close by a bunch of interesting things and it's still kind of a mysterious brain area but when I learned about pgeo waves I thought pons, geniculate occipital because occipital was most commonly associated with visual cortex I thought it was the origin of the visual component of dreams

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 or an early morning later in sleep I should say and early morning dreams seem to be cobbled together from disparate experiences you walk through a door and suddenly it's a completely different context and landscape

I like this idea but it makes intuitive sense it makes biological sense it also gives me something to talk about to the medical students next quarter when I talk about pons it's right below the locusarulus it's called the sub-serulus their glutamatergic it's also called sld sub lateral dorsal nucleus so I love it so note to any aspiring neurologist there's a vast landscape of yet to be undiscovered structure and functions in the pons

you want to work on something that is sure to reveal something novel work on the pons because it's in every textbook it's clinically very important structure sadly gliomas and other cancers of the brain can sometimes can often surface in the pons but we still know very little about it

I read a paper this last year 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 them math problems

they'd whisper in their ear while they were in REM sleep you know what's two plus two and people would say even though they were paralyzed apparently they could still move their mouth because they'd say for 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 up that what do you think and I don't know the authors of that study and listen if ever I say something wrong

it's great on this podcast because someone will tell us in the YouTube comments it's one of the great uses of YouTube comments but I'd love to know your thoughts on that study I mean is that just kind of a 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 intriguing and interesting and might relate to this paper I talked about where we said different areas of the brain can be in different states at the same time so lucid dreaming is another thing we can't ask animals to do or can't ask them if they've done it but we can certainly ask humans to do it and some people can do it really well and it would be really interesting to see in those people who could lucid dream really well

whether they spend more or less time in this asymmetrical state where one area the brain is in one state and another area the brain is in another and it might be that those people can respond to questions during REM sleep best are those that have the most asymmetry

or dissimilarity or dissociation between subcortical and cortical structures or it might be that they're the ones with the most symmetry we don't know I do worry a little bit about lucid dreaming because people are it's a fad people are really excited about it and to be able to remember when dreams is fun often unless they're nightmares but it's really interesting or to be able to direct one's dreams if they are a nightmare 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 locus realis from calming down or the serotonergic system from silencing like it should and maybe what we're doing during this state is yeah we're activating the learning and memory structures

but in a way that's maladaptive in terms of the erasure that we need to do so maybe one of the reasons why most people don't remember most of their dreams is for good reason your hippocampus is in a state where it's not writing new memories in fact it's writing out

it's the memories it learned during the day to the cortex and it's immune from incoming new information so maybe lucid dreaming is bad because you're activating the hippocampus in a way that's writing new memories and it might be really maladaptive for things like you know PTSD on the other hand let me just argue myself right out of this when I used to have a repeated nightmare when I was a kid my mother who was so wise would tell me well listen just next time you're in that dream

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 and that monster comes after you I'm gonna run away no 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 what could you do that's different so I came up with I'll I could turn around and punch it and then I was just 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 you know or touch the monster in any way but I did have the courage to turn around and look at in the eye and say no that was enough I said no and that was enough to knock me out of that ret of that dream so that I never had it again I never had that same dream again and in fact it gave me a piece 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 ret one thing that happens with people with PTSD is they have the same repeated

horrible nightmare which is often a reliving of the day's 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 ret of reliving that event and just change it

you know and you could probably practice that during wakefulness and rehearse the event that happened that was so traumatic and then just introduce a new element like you know now I'm safe now you know the sound that was associated with that really traumatic thing I should now associate with something else and next time I have that dream I'm going to change it so that sound is now this new thing that it should be associated with safety

and that might be enough maybe I hope to knock you out of that repeated nightmare and maybe even start to want to pack the recovery because if you can calm down about those nightmare states of sleep then maybe your locus aryl is

which is involved in stress can also relax and you can do the erasure parts that need to be done I love it I seem to recall a paper and I'll have to find the reference and send it to you we will also put in the show no captions that described a protocol essentially matches this idea

and well I think what they had people do is either cue themselves to a particular smell or tone and wakefulness then to try and recall a recurring nightmare then during the night sleep they had the tone playing in the background which would then cue them to the wakeful state they're still asleep mind you but in the pseudo lucid or lucid state and then trying change some variable as you're describing some either look the predator in the eyes or do something different

and then in the waking state take a little bit of time to try and script out a different narrative altogether and it took several nights as I recall or more but that they were able to escape this recurring nightmare it was like a week or something so you're familiar with the study it's a beautiful study I loved it we will put a reference to that I need to revisit that say it was pretty recent but I need to dive into it again because I think I didn't go as deep into it as I should have

no no but the one thing that you said many right things but one of the things you said is that they were able to cue the dreamer when they knew and they were going to REM sleep and then they played the sound or had the odor now when you're normally asleep alone in your bed you're not going to be able to cue yourself but it might be that rehearsal enough before you go to sleep is enough to you know help cue you to that repeated nightmare

remembering what the nightmare is and then figuring out how to cue yourself to do something different for years I had the same recurring nightmare over and over and over again and it was so salient and so clear and I'm not going to share what it is because it's it's not that it's that disturbing it was just I think it was the emotional load of it and just how salient certain features were like one person in

who is a real life person had a particular clothing on and it's like and that just served as this cue and I don't know if I ever did any direct work to try and deal with it but now it almost seems silly to describe it oh yeah well dreams are usually silly to describe it but you're emotional system

yeah 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 Lucas Sirulius is ideally suppressed so we can't release nor epinephrine we can't act out our dreams this during these very emotionally laid in thoughts

and storylines during sleep this is almost I start to sound like a little bit of a built-in while sleeping trauma therapy because most trauma therapies involve trying to get people into states of counter to what most people think you actually want to get close to the trauma in terms of the narrative

that's right I'm trying to suppress the emotional activity of it or I guess that's the motivation for ketamine based therapies for trauma or I've also heard and this is still perplexing to me that other waking based trauma therapies involve taking people the other way making it very cathartic take them to the peak of the emotional response but then allow that to finally cycle down into a more relaxed response so please if there's anything about Lucas Sirulius and dreams that can help people

basically extinguish traumas or traumatic features to real life events we definitely want to know about them yeah well I think one of the things that people fought might help after a trauma like a school shooting or whatever you know car accident is to talk about it

and 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 you back down it brought them up and continued to reactivate the emotions of it but then didn't you know emphasize the safety effect that it's over or help them work through how they might avoid it again in the future to calm the sympathetic nervous system down again before they went to sleep

and in 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 Lucas Sirulius 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 then a reinforcing the emotionality of the trauma

and I think the key to that again is the absence of an orphan effort and so even though the emotional system is in high gear without an orphan effort you can actually divorce those highly activated emotions from the cognitive parts of the memory that you have just written out in that end to you stage of sleep when the sleep spindles are going

so so you've just now consolidated the information that you'll need to survive and to you know to make that adaptive and now you need to divorce from that schema and from that semantic parts of memory the emotional part because whenever you remember something 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

and you're going to bring back you know the heart rate changes and the sweating and and all of that you want to be able to remember all the parts of it and even remember that you were traumatized and that you did cry and that you did have 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 dramatic memory because you're basically putting yourself through the same trauma which is what people with PTSD have

and you 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 not long are not able to be divorced because the neuro-frontal system is not down scale during REM sleep that REM sleep serves to instead reinforce and in fact amplify the emotions because your emotional system is up, the locus paralysis, hi, re-sowing in every night the emotionality of those memories and with the memory itself

you told us a lot about locus relias in noraponephrine from locus relias is there any role for noraponephrine epinephrine in cortisol released from the adrenals my understanding is that noraponephrine in epinephrine will not cross the blood brain barrier which is probably why we have a brain-based noradrenergic system so that's a question I should ask you are there other sites in the brain where noraponephrine is released from or is it just locus relias

so there are seven, nine different adrenergic, yes there's nine different adrenergic structures I'm sorry I didn't ask but it just occurred to me that in some cases like with Raffa there are other sources of serotonergic drive in the brain but Raffa is like one main that's the one that goes to the cortex and the locus relias 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 do what you need to do so yeah so there are lots of other noradrenergic nuclei

but the locus relias is the main one that projects all over the brain actually the only place that doesn't project is the dorsal stridum you talked about ventral stridum and addiction the dorsal stridum is the only place the locus relias doesn't project to and that's involved in procedural learning

motor learning the kinds of learning that take over when you're hippocampus for example is compromised by lateral if you don't have a good hippocampus you can still do procedural learning and it's great it's a redundant system and so if your locus relias is not working if you don't have it anymore you can still do if you don't have a good hippocampus you can still do learning through this dorsal stridum structure so it might be for those kinds of learning functions

sleep deprivation where you never let the locus relias stop firing is okay because it doesn't have any receptors for noradrenerfrane anyway so yeah and what about bodily like adrenals yeah you know I offer mine people is 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 nor epinephrine 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 adrenals do great things they constrict our blood vessels causing higher blood pressure which help blood rush out to all the extremities that need blood you know our muscles for example for running away from the lion or the tiger or eating a grand deadline or catching a train yeah the adrenals help our hearts from faster our muscles get perfused with the blood it needs

it diverts blood and everything away from our parasympathetic system which is rest and digest we don't really need to digest that croissant when we're running for a train we can do that later so it's doing really important things what we don't know because it doesn't cross the blood brain barrier is how that affects the brain and whether our if we can independently activate our adrenals when a time when our brain thinks

that we should be fine and calm and asleep how our brain detects that and is it a feedback through our heart is racing and then our brain stances is what's going on my heart is racing and then wakes us up and then our hearts were racing together with our brain racing we just don't know the answers to these questions yet there are some good 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 ongoing

and still to do I'd love for you to tell us about some of the work that you're doing more recently on the relationship between sleep and opiate use with your all 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 benzodiazepines 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 our sleep is disturbed our sleep is terribly disturbed and the amount of sleep disturbance predicts relapse behaviors

and you might think well of course you're going to relapse if you can't sleep because opiates calm you down will the reasons why opiates calm you down is because the locustarilus again the loose spot is covered with opiate receptors and that are normally really responsive to our endogenous opiates

and so what what happens when we're pleased for example or laughing or whatever and doggies opiates activate those receptors in the locustarilus and calm it down and it actually suppresses locustarilus 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 exogenous opiates is that they really strongly bind these receptors on our locustarilus

and if you take and exogenous opiates again and again like you're recovering from surgery for example take these pain medications is that our locustarilus struggles to do what it's supposed to do which is keep us awake and learning and concentrating on things

so it will down regulate it will internalize these receptors that are normally only occupied by endogenous opiates and it will do this it will change our genes that are associated with producing these receptors so you actually have very many fewer receptors so the locustarilus 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 exogenous opiates there is not enough of your endogenous opiates to be able to occupy those few receptors that are there

and our locustarilus 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 exogenous stressor that adds to that and it also activates our locustarilus there's nothing to calm it down again and so it just keeps firing it disturbs our sleep and that's why maybe sleep disturbance is an indicator of a hyperactive locustarilus

and such a good predictor of relapse behaviors because nobody likes to live in that high stress state and they will do anything to get back to normal so the problem with taking these drugs is that it leaves you excited or sorry excited relaxed and happy

but then when you come off of it you're worse than when you wear a 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 what I say

certainly central nervous system depression I mean sleepier less motivated lower mood yeah I mean our locustarilus is actually it's a it's 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 endogenous opiates can properly calm our locustarilus once that they have been tamped down by exogenous opiates but that would be really one way that you can access the sleep disturbance so we talked about sleep and the importance of sleep in terms of learning and memory the importance of the structure of the 90 minute cycle for all of that

so you can imagine if your sleep is disturbed by too much locustarilus activity the in 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 that as involved the drugs becomes compromised

and so that's something that tanya lu goes in collaboration with Pamela Kennedy at UCLA that we're looking at how is learning and memory affected by the sleep disturbance if they're way we can in animals that are coming off of opiates can we restore their sleep to normal so that then they are less likely to do relapse kinds of behaviors

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 on this podcast of breathing extra sleep

meditation whatever it is that helps you calm yourself before sleep yeah right would just would facilitate not just sleep but perhaps even accelerate the recovery and and shorten this period of withdrawal which from the questions I get and from what I hear can be absolutely brutal yeah so I can imagine I had to take opiates for I only took it for three days after giving birth to my first son I think second son one of them and and just I just said after three

days this is enough I'm just going to try Tylenol and so I I weaned myself not weaned I just did a sudden sharp cut off and even though I felt I didn't get the high of opiates when I was taking the Tylenol coating when I went off at boy it was like PMS times 100 I was so anxious and upset little things

thankfully only last few hours but if I had taken it for a week or two weeks who knows if my endogenous opiate receptors would have been permanently down regulated and I would have been an addict you know and I think I would have been addicted I shouldn't say an addict there's negative connotations it's just a very physiological state so no judgements 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 taught us a tremendous amount in in a relatively short amount of time about the architecture of sleep the different phases relationship between sleep and dreaming in this incredible structure locust

really isn't so happy we also got into the ponds that just delights me because we rarely talk about the ponds on this podcast but such an interesting structure sex differences that are important creativity and problem solving and trauma sleep spindles just such a wealth of information

and much of it that's actionable for people so first of all I want to say thank you for taking the time to sit down and have this conversation that so many people are sure to benefit from I also want to thank you for doing the work you do even though I'm a fellow neurobiologist I think that it's not often that we take a step back and realize that it's really the work of hard thinking hard strongly motivated

PIs and stands for principal investigator by the way PIs like yourself 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 implement they 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 and you thank you for being an amazing interviewer you brought a lot out of me in a coherent for fashion that normally I can't do when I'm speaking in public I don't know about that I heard your lectures and they're superb will direct people to some of the other ones

thank you and I also want to put a plug in for graduate students in general in the key and amazing role that they play in research I am a P.I. as you said I used to be a graduate student in 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 I'm a P.I. I 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

who actually contribute 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 postdocs

and listen and to the major institutions 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'll 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 Poe I hope you found it to be as informative and as actionable as I did in fact I'm already implementing the

regularity of bedtime plus or minus half an hour in order to get that growth hormone release and I can already see both my sleep scores improving and my feelings of daytime vigor and focus and other markers of sleep health improving as well

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content of the uberman lab podcast but much of which is distinct from the uberman lab podcast content again that's huberman lab on all social media platforms thank you again for joining me for today's discussion with Dr. Gina Poe all about sleep and its relationship to mental health physical health and performance and last but certainly not least thank you for your interest in science