How the Brain Controls Sleep: Sleep Neuroscience Explained

[00:00:00]foreign welcome I hope uh some people out there ready to talk about sleep um today I'm going to be talking about how sleep Works uh what sleep is um why we need sleep what it's important for and most importantly the Neuroscience of sleep so um I'm just going to kind of jump right into it and if you have any questions throughout this episode please do not hesitate to ask I'll be watching the chat and uh seeing you know what you guys are uh saying in there um so sleep is basically I'm going to claim that sleep is a set of dynamic brain states that allow the brain to repair damage restore function and reorganize neural connections and we'll get more into what exactly that means in a minute but um just as kind of a quick overview of what sleep is so that makes it sound like it's all about the body but in reality sleep is also or sorry it's all about the brain but sleep is also for the body as it I just said um and we're going to be mostly focusing on what it does for the brain and how it works in the brain and I think there's there's strong evidence that sleep is primarily for the brain so um that's kind of the overview but another way to look at sleep is kind of behaviorally so if we're going to look across the animal kingdom and try to identify when animals are asleep the first way to do that is through behavior and of course you know that when you go to sleep it's you have severely reduced vigilance and awareness and um yeah you're not responsive and different sleep stages are more or less responsive we'll talk about that later but they're more responsive than a coma or anesthesia as you know you might imagine it's it's possible to wake up from them once the stimulus reaches a certain intensity but um there's also not only this lack of responsiveness but also an absence of goal-directed behavior so that's pretty obvious you know uh you're not getting up and moving around or doing anything goal directed while you're asleep um and most other animals don't although uh interestingly animals like whales and and dolphins sleep with only one half of their brain but that's very different than how humans do it so we're going to focus on um on mammals particularly land mammals and humans um so physiologically uh sleep is characterized by different EEG patterns so this is different patterns of electrical activity occurring in the brain and we'll talk more about what those are in the specific stages of sleep um but just for now there are two different uh primary stages of sleep REM and nram and they have different electrical activity associated with them there is also decreased body temperature while you're sleeping and there's actually a a fluctuation that occurs in your body temperature your core body temperature during sleep a particular pattern that happens where it goes down until you reach a certain point in the night and then begins to come back up um but again this is just a big overview of what sleep is and sleep is also a state where our muscles are limp and inactive so we have what's called muscle atonia so that's kind of an overview of what sleep is we're going to get deeper into all of this stuff throughout this episode um I apologize for my voice uh starting to lose it for some reason I think I'm a little bit sick uh but you're we're only you know doing this virtually so don't worry if I cough you're not going to catch it obviously um but anyway so before I move on I just wanted to mention that some of the sources that I'm using for this video for these uh what I'm going to be talking about in sleep um the main paper that I'm going to be referencing is one that was just published last month in nature and Neuroscience it's a very prestigious journal and it's called neural orchestration of sleep and wakefulness the first author is Suleiman I believe BB Suleiman um so yeah that's a 2022 nature paper and I just want to mention at the outset that a lot of what I'm going to be talking about has been corroborated in humans but the specific neural circuitry that we'll touch on later in the episode is mostly um it was best characterized in mice and rats and so rodents rather than human brains but I'll talk about um findings that seem to corroborate in in humans as well so I just want to mention that from the outset um okay and then before we get back to sleep I just first want to say thank you all so much for watching or listening um and to uh V ants in the chat uh this is indeed a live um recording right now so if you have any questions go ahead and ask them um sorry but uh anyway I wanted to say thank you all for so much so much for listening and watching and supporting this show the reason I'm bringing this up right now is because this channel is actually now a hundred percent independent um you may have heard me in previous videos talk about that uh this channel was supported by the diamond mine Foundation charitable organization but we're no longer associated with them anymore no hard feelings nothing bad between us but um but uh it's it's just really helpful if you guys can can give your support because like I said we're now 100 independently funded um so so there's some free ways to support us by subscribing to this channel liking this video posting comments and questions as well as subscribing to the podcast version of sense of mine and giving it a five star rating um so throughout this video uh please share any questions or comments and I will try to answer them to the best of my ability um noting that I am not actually a sleep scientist uh I'm just a neuroscience Enthusiast I've read a lot about this and uh trying to give you what I understand from my reading of the literature um so I'll try to answer questions the best of my ability if I don't know I'll say I don't know but don't hesitate to ask and also I want to just encourage you if if anyone's um really wanting to contribute and really help um uh you can do a super chat I Believe by um and basically donate money uh while we're doing this live recording or do a super thanks afterwards those are really helpful eventually uh gonna have a patreon going and all that but for now the free ways to support are super helpful so subscribe and like and post comments and okay that's it I'm not going to talk anymore about that kind of stuff uh until maybe the very end let's get back to sleep so what is sleep for why do humans why do animals sleep so this was for a long time and still kind of is a big mystery um in neuroscience and uh sleep science generally so there's multiple hypotheses of why we sleep and they all pretty much Converge on the idea that sleep is for brain repair and neural reorganization so like I said before it's for restoring the brain repairing damage and for reorganizing neural connections so a lot of processes having to do with synaptic plasticity strengthening and weakening connections but it raises the question why do we need to go into this sleep State why do we need to shut down normal cognition to go into this reparative restorative reorganizing state and um that that's a really important question because if you think of it in an evolutionary sense of survival it would be really disadvantageous to just kind of go offline for hours at a time and there are animals that sleep for the majority of the day so there has to be a really important process going on something that that adds to our adaptive or our fitness evolutionarily and there's there's some interesting ideas about that but basically I think the most compelling idea is the fact that unlike other cells in your body your brain cells neurons specifically don't replicate themselves so um like your liver cells and your skin cells and most of the other cells of your body do uh regenerate they replicate themselves so they make more cells and they can make repairs in that way and get rid of damaged cells but in the brain you only really have a set number of neurons now there is some amount of neurogenesis new neurons being born but the basic idea is that because the these neurons can't regenerate can't replace themselves they have to have a time to actually do all this repair and important reorganization and so sleep is is seems to be necessary it seems to be a state that we have to go through to to keep our brains functioning healthy um Okay so if we don't sleep we'll die that's kind of the bottom line of this um the Sleep kind of always wins out overweight unless you have a very rare um genetic disease called familial fatal insomnia there's very rare circumstances where people really can't sleep but sleep seems to always win out eventually over wake um and just as a side note if you sleep less than six hours a night there's a correlation that says you have a 13 higher mortality risk so that's pretty significant in terms of um raising your chances of dying from all cause mortality that could have to do with getting in car accidents and other um you know results of poor cognition due to sleep deprivation but that kind of brings up a really important question what are the benefits of sleep if sleep is so important What specifically is it doing for our brains and the first thing that you might remember if you've ever thought about this kind of thing is memory sleep is really important in the consolidation of memory and skill learning so I think the coolest example of this um is in rodents in rats actually there's these experiments that show that if you teach a rat to do a maze while they're doing that maze there are specific collections of neurons in their hippocampus called Place cells not really important with the brain regions right now but there are these neurons that show a specific pattern of activity corresponding to that rat solving the maze so these are basically the the rats representation of where it is in the maze um just saw your your question Monica in the chat about how is sleep deprivation and increased risk of stroke related um there we can get back to that in a second but it will have to do with um risk higher risk of cardiovascular disease and things like that um but just completing this thought on why sleep is so important for memory um so while these rats go through this maze there's this pattern of activity corresponding to them solving the maze when they go to sleep specifically during nrem sleep that pattern gets replayed in the hippocampus really fast about I think it's about seven times faster than during the initial encoding when they're going through the maze but it's that same pattern and it not only goes forward but also in the reverse Direction so during nrim sleep these rats and humans as well we are we are replaying memories and consolidating them making them stronger and one way that this happens are the main way that they think this happens is um there's a communication between the cortex and the hippocampus and the hippocampus is really where we we initially store memories and then what happens during sleep is it's talking to the cortex and helping to lay down those memories in the cerebral cortex um we're going to get more into neural circuitry and those sorts of things later um but uh this is just kind of to to let you know that memory really benefits from sleep there's uh evidence of of enhanced recall memory recall and and kind of all aspects of memory are um important or are benefited by sleep the second type of benefit is more physiological and it's down at the the cellular level in the brain um molecules that we use during the day that are broken down during the day are re-synthesized when we're sleeping so that is another function of sleep is kind of restoring these macromolecules that we used during the day but maybe more important is during sleep there are a lot of DNA repair processes going on so throughout the day and and just normal activity can damage DNA and you really don't want your DNA to be damaged that can lead to all sorts of uh problems diseases cancer um so when we're sleeping part of what's the benefit is is that sleep is repairing or it's facilitating processes that are repairing DNA um then uh it also helps with something this is really cool waste clearance from the brain so throughout the day we kind of build up metabolic waste we build up um these toxic metabolites in the brain and sleep helps to clear these out it's kind of like uh the the analogy that sometimes gets brought up is people um in an office building they go away from the night and then the uh the cleaning crew comes in and clears out all the waste empties the trash bins and all that uh cleans the floors and everything then you come back in and it's clean in the morning that's kind of what uh sleep is doing for your brain but interestingly one way that this happens is that during nram sleep there's a specific pattern of activity going on in the brain uh that causes the the space between cells called the interstitial space to expand and this allows a cerebral spinal fluid and I believe Blood also to mix with the interstitial fluid and then wash out the toxic metabolites from your brain um so we'll talk more about uh about the kind of activity that promotes that in a little bit but um another kind of benefit is just kind of stacking up the the different benefits of sleep is to the immune system so sleep is really important for keeping your adaptive and innate immune system both the major arms of your immune system functioning well and it does this mainly by regulating hormones but um you can see this by uh there's some studies that show that people who have been given nasal drops that are infected with a rhinovirus a cold causing virus um they're more likely to actually develop a cold if they hadn't slept the night before or in the if they had been having poor sleep I'm sorry they've been having poor sleep leading up to the actual study or to the actual um infection they have an increased risk of developing a cold um and I'm just kind of skipping through these benefits because there's so many I'm trying to hit on the the most important ones and get to the the Neuroscience as quickly as possible um but you know it's uh really important to mention that sleep is is also beneficial for babies and children especially for the developing brain because there's so much brain growth and new synapses being formed in babies and and children but especially in really young babies and sleep is important for uh the maturation and wiring of neural circuits um so anyway so that that kind of covers the the broad benefits of sleep and um and uh yeah I think I think I'm gonna go on from there and move into we just talked about that sleep is so important for babies and they actually sleep a lot more disproportionately more than adults and there's a question there this is actually not just with babies but with smaller animals smaller mammals sleep more than larger ones so elephants sleep only about four hours a day and um I don't know why this example is coming up in my mind but armadillos much smaller animal are um I think they sleep about 18 hours a day and so that's that's a huge difference and that leads to a question why do smaller mammals sleep more than larger ones and there are different ideas about this and I will say that this pattern isn't perfect because there are um examples of other factors other than just body size affecting how much an animal sleeps like the latitude that that animal's at but in general larger mammals sleep less than smaller ones and one theory that was uh proposed by they're actually physicists Jeffrey West and Van Savage I've uh I have an interview with Jeffrey West on my show if you're interested he actually talks about this theory of sleep but the idea is that metabolism metabolism is the important thing the brain uses energy and um an interesting fact about bigger mammals bigger animals is that their metabolic rate per gram of tissue is lower than smaller animals so effectively that means that larger animals are more efficient at bringing blood and nutrients to cells throughout the body so they're more efficient they use dis they use less energy per gram of tissue so that is also true for the brain as brain size increases the metabolic rate per gram of tissue also decreases so larger animals this is kind of where where it comes together larger animals don't need as much time as sleep compared to smaller ones because their brains are more efficient at repairing damage and doing those processes we were talking about that sleep is so important for so that's and this this sounds a little bit too simple but West and Savage the the people who the guys who came up with this Theory um they modeled this with an equation and the equation actually fits the data very well um so there's some compelling uh reasons to believe that metabolism is really the driving force for uh why animals of different sizes sleep for different durations now babies babies are an interesting case because of course baby brains babies brains are smaller than adult brains so of course we would expect them to sleep more than an adult but if you plug in the numbers it turns out that babies younger than about two and a half years old sleep way more than you would expect based on that theory so they sleep disproportionately more even when you take brain size into account and what the what West and Savaged uh hypothesized was that maybe they need more sleep this extra amount of sleep because their brains are undergoing this incredible amount of growth and synapse formation in such a small amount of time um so the adult brain is relatively stable compared to baby brain even um a child's brain even though it's it's very plastic and dynamic and going and um more Dynamic than an adult brain the baby's less than about two and a half years old are extremely um their brains are are growing like crazy so when they factor that into their equation they found that it did fit the empirical data so I just I find that really interesting as this this kind of simple idea about metabolism controlling the the duration of sleep there are a lot of other factors in there um there's uh genetic differences um you might notice that some people need more sleep than others and um it's so that it's not quite that clear-cut but on average this seems to account for those those differences between animals of different sizes and vans just said um perhaps larger animals also need more time awake to get enough food to maintain caloric intake um oh that's you know that's a good point too but again they are more efficient per uh gram of tissue so and I have to we have to think about that uh how that would all work out but um and then let's see Bruce asks are there any small animals that sleep like whales and dolphins only half the brain asleep at a time as another way to be efficient instead of growing larger that's a really great question I don't actually know I know um I I saw this talk or he was talking about how um I can't remember exactly which animal it is but it was a small I believe it was a reptile and if you placed it in a cage next to a snake and the snake was on the other side of a wall it would only sleep with the half of its brain that was not facing the snake so it's it was a prey animal and it was like worried about the snake so half of its brain is staying awake and the other half isn't now as far as we know humans can't sleep with only one half of their brain at a time and I'm not really aware of I don't even know which animal that was off to look that up but um but yeah I think there are some limited number of examples of animals that sleep with their brain half half their brain at a time good question okay so this kind of uh literally sleeping with one eye open yeah good point yeah um okay so next we're gonna really get into how the brain actually controls sleep and um on the broadest level uh there's this idea of the two process model of sleep and I'm actually gonna just show this graphic um because I think it's it just helps explain this and we're not going to spend too much time on this particular um idea but it is something that I think is worth knowing about um hang on let me just pull that up but basically there's this idea that there's these two different processes that are influencing the duration and timing so when you sleep and how long you sleep and there are circadian rhythms and sleep homeostasis and circadian rhythms are these rhythms that happen once a day once every 24 hours and they kind of happen like clockwork it's these biological processes that are happening every 24 hours whereas on the other hand there's sleep homeostasis and this is basically just this idea that the longer you've been awake the more you feel like you need to sleep so uh that's that's sleep homeostasis and circadian rhythms and these two processes actually kind of um uh oppose each other and I'm gonna find that graphic really fast um sorry for the the delay here um but it's Okay so okay so I hope everyone can kind of see this um this is this two process model of sleep um this I got this graphic from Precision Nutrition but it's basically showing on the bottom you're seeing a circadian alerting signals so that's that circadian rhythm um kind of waking you up or or influencing your your level of alertness throughout the day and then at the top you're seeing sleep drive so that's that sleep homeostasis how long you've been awake um is proportionate to how much you need to sleep and these work together to um to basically uh make us feel more or less sleepy and if anyone wants to know more about that I can explain that more but um I'm just gonna kind of move past it because I want to get into the real neural circuitry of sleep um Okay so so the thing about sleep is that it's it is it may actually be so deeply a part of the brain that it's it may be the default state of the brain and we'll return to that in a bit but the point of mentioning that is that certain brain regions actually actively keep us awake and their activity is required to wake us up from sleep so we're not necessarily just uh naturally awake there are these wake promoting brain regions and the most important of these is the lateral hypothalamus and I'm going to share a picture of the lateral hypothalamus because I I don't want to get lost in all the jargon and um it's uh it's basically one of the only brain regions we're going to be focusing on throughout this episode so uh should at least show it you know once um Okay so here's that um okay so this is an image of the the hypothalamus and actually um this is the brain stem coming up to connect with the hypothalamus in here and then up above is the thalamus but for anyone listening to this it's basically in in the center of the brain above the uh brain stem but below the thalamus and what the hypothalamus really is is this collection of nuclei this collection of little tiny brain regions basically and um when it comes to wake the most important ones that are actually keeping us awake keeping our brains in that wake state are the lateral hypothalamic neurons so this image these these purple ones on the on the right over here you don't have to memorize this image obviously but just just as a visual to to give you an idea that the hypothalamus is organized as these these nuclei these specific little regions um the lateral hypothalamus is important because it when it's activated it signals to the a couple of brain regions the locus ceruleus and the thalamus and um again don't have to memorize these brain regions the point of this is that the lateral hypothalamic nuclei send these these uh excitatory projections to these other regions that then send it out to the rest of the brain um and and the locus ceruleus is important because it produces noradrenaline and that's a molecule that's a neurotransmitter in our brains that makes us feel awake and part of the way it does that is by keeping the cerebral cortex active that that area of the brain that folded convoluted um you know thing you think of when you you think of what a brain looks like it's that outer layer of the brain and it's really important for all kinds of cognition perception planning thinking feeling emotions um this is a really just generally important brain region for that kind of higher cognition and the locus ceruleus keeps that active but it's not only the locus ceruleus um there's this there's also this interaction between the thalamus and the cortex and um for now we're just going to focus on the fact that these lateral hypothalamic neurons are keeping the cortex active but they're also sending projections to our our body through our spinal cord and keeping our bodies active um so that that's kind of the the basic idea of of what the lateral hypothalamus is doing to keep us awake on the other hand it is also inhibiting brain regions that put us to sleep and we're going to talk about what those are in a second but um there's this you know you can think of it as it's not only waking us up keeping us alert keep increasing our arousal but also tamping down inhibiting the activity of nuclei of brain regions that are involved in putting us to sleep so that's kind of the basic picture of um of uh the Wake State the awake state so then when we do finally fall asleep sleep is uh always begins with nram it always begins with nram sleep and I'm going to show that um so this is a uh what's called a hypnogram and this shows a single 90 minute sleep cycle and that's typically how long an individual sleep cycle is we go through these our brains go through these uh specific patterns and um it lasts about 90 minutes and then we have roughly four to six of these per night but what you can see is that we start out in Wake that's a w and then we fall asleep and we actually it looks like in this image that we're going through REM but we don't uh we go into uh nram sleep so that's the N1 N2 and N3 and essentially what's happening is we're going deeper and deeper into nram sleep and um just to give you an idea just to show what the difference between these different sleep stages are when you look at them on an EEG so this has been like EEG has been one of the most important tools for actually um uh for me for Sleep science for for studying sleep and um what you'll notice about this graphic is that the Wake State the first thing to notice is the Wake state looks kind of similar to both stage one and REM and to REM sleep um and that'll come become more important later but it looks very different from nram stage 3 which is that deep sleep where we spend most of the time of nram in and that um what you're seeing are these big waves these high amplitude slow uh waves and this is what's called slow wave sleep slow wave activity of nram sleep and what that's telling you about what's going on in nram sleep is that there's massive numbers of cortical neurons that are synchronized they're firing in synchrony and creating this this massive um uh these these big slow waves these of electrical activity versus during wake uh you're seeing a much more kind of mixed up uh EEG it's a lower amplitude faster waves um and similarly with REM um but so you can see that that nram is very different from the Wake state in terms of what the brain is doing and again this is driven by these uh cortical neurons firing in synchrony in large numbers okay so I'm gonna stop sharing that and uh check if um okay so I got some questions here uh let's see is there any study of correlation of sleep duration with factors like rate or sorry race height slash weight gender Etc that's a great question that's something I don't really know much about um I would assume that that maybe your your genetic or ethnic background has something to do with that uh weight yeah I'm sorry I don't have much um much about the demographic stuff if anybody does it'd be really interesting to know um let's see anything else is it true you can learn in your sleep like hip hypnagogia um as far as I know it's there's not really any evidence to support that you can actually learn in your sleep although there are some experiments in mice where they're able to enhance memory consolidation by uh stimulating particular neurons while they're asleep but in human and I don't think that that's really translational to humans um but yeah I think uh probably no is the best answer to that question let's see I know certain stages of sleep the brain speeds up and repeats and Smooths out actions at higher speed like playing a piano piece is smoother after sleep yes yeah that is related to um the uh the skill learning the the uh hippocampal Replay that we were talking about earlier about the benefits of memory yes that's that's true um and then yeah a lot of okay cool yeah so I don't think you can learn a language in your sleep although if anybody knows if that's true I'd love to do that I'd love to to uh learn another language um okay so we just talked about what nram is and um wake what wake is and wake is inhibiting the brain regions that put us into nram sleep um but when we're talking about what nram is that it's this this highly synchronized activity of the cortex uh of these neurons firing in synchrony that's actually being driven by activity in the thalamus the thalamus is just above the hypothalamus and it's it's a really important brain region it's like a sensory relay station but for what we're talking about it seems to be actually generating the the kind of um oscillation the kind of activity that it then um tells the cortex to to uh have that same oscillation that same frequency that uh synchronous activity we're just talking about so the point of mentioning that is that there's these Thalamus to Cortex uh thalamo cortical bi-directional connections that um mediate those those oscillations that occur during nram sleep excuse me I'm just going to drink some water you can hear my voice going away okay excuse me um all right so similar to the wake related brain regions the Wake promoting regions there are there is a primary sleep promoting brain region and this is the pre-optic area of the anterior hypothalamus so we're I'm not going to even show that image again I'm just going to say this is another one of those nuclei a different set of nuclei but it's also in the hypothalamus and it is important for putting us to sleep so when that brain region is activated specifically if you're interested Gaba releasing neurons um that's not important for our purposes but um when you stimulate these neurons they can promote nram and so they can make us more likely to fall asleep and there's an interesting um interesting finding that the firing rates of some of these neurons in the pre-optic area correlate with how much uh with that sleep pressure accumulation that sleep drive that we were talking about earlier that feeling of of sleepiness essentially um so there are neurons whose firing rate correlates with that that sleep pressure accumulation now like we just talked about these neurons this pre-optic area are normally inhibited by lateral hypothalamus neurons and that's that wake promoting brain region um so when when that region kind of releases the brakes we can turn on uh nram sleep with turn on REM sleep I want to emphasize though that I'm focusing mostly on these hypothalamic circuits there are other circuits there are other important brain regions that are really crucial for sleep but for the purposes of some Simplicity I wanted to focus on these because these are kind of the primary wake and sleep promoting regions um and of course they only do what they do based on their connections to other brain regions um one interesting one I want to mention that is not part of this this hypothalamic circuit is in the basal ganglia and the basal ganglia is a set of regions kind of at the center of the brain I'll just show you on my little brain model over here um and I guess not because it doesn't have the right let's not cut on the right plane but the point is there are these regions that are really involved in movement and in uh dopaminergic rewards so if you know anything about dopamine the this is a region that is super important in that kind of reward and uh prediction error process but it's also important for movement and interestingly there are these adenosine receptors in the basal ganglia and adenosine is a molecule that kind of builds up from the time we wake up in the morning to the time we go to sleep it builds up over the course of the day and it's kind of a correlate of that sleep pressure need and when adenosine binds to the to the receptors in the basal ganglia it that helps to generate mrem's nram sleep as well um so that's just another way of seeing uh that there's multiple circuits and that we can we can promote sleep by by stimulating various uh regions but another thing about adenosine that's interesting is that adenosine receptors are um blocked by caffeine so when you drink coffee caffeine gets into your brain and blocks these adenosine receptors and that's the main mechanism of how caffeine keeps you um awake keeps you from falling asleep it's blocking these adenosine receptors they're important and REM sleep so that's pretty much all I'm going to say on nram here um so uh yeah let's let's now move on to nram transitioning into REM and I'm just going to say a little bit on what REM is so um behaviorally REM is actually thought to be one of the is probably the deepest um deepest sleep that we go into it's sometimes called paradoxical sleep because the brain looks a lot like it does when it's awake in terms of the EEG like I showed in that graph that the EEG looks very similar to wake a little bit different um but a lot of the same regions that are active when we're awake are active when we're sleeping except we're effectively paralyzed our brain turns off uh the ability to actually activate our muscles so we don't act out our dreams and it's it's thought that dreams especially vivid dreams are mostly happening in REM sleep it's kind of um there's it's kind of another mystery about RAM and nram of why do we have these two different stages of sleep um what is each of their purposes it seems like they both have to do with memory consolidation um and they may both have to do with that uh kind of restorative and damage repairing function but nram seems to have a larger role in both of those there's various ideas about why we have RAM and nram but I just want to mention some of the basic characteristics of REM so it looks kind of similar to the awake brain but we're actually less responsive than when we're in nram sleep and we're effectively paralyzed if you're wondering REM stands for rapid eye movement and um uh that's because in certain parts of REM we have these rapid eye movements and limb and muscle twitches um so that was kind of how they first identified it was somebody was uh apparently asleep but their brain activity looked like they were awake and their eyes were moving around underneath their eyelids so that was why it was called REM sleep in the first place and then nram is just non-rapid eye movement sleep Okay so moving into REM um REM sleep is there there's this idea there's this model of how REM uh works and it's basically comes down to two different kinds kinds of neural circuits in the brain there are what are called gatekeeper circuits which are thought to prevent uh us from going into REM when we're in wake and nram so there's circuits that are just there to to guard the gates of REM keep us from going into that REM state and then there are separate circuits that seem to initiate and control REM while suppressing wake and interim and these are called the generators and maintainers so we've got The Gatekeepers that keep us from going in and then the generators and maintainers that set us into rim and then control and and regulate REM sleep um if you saw the thumbnail of this video you probably noticed that uh I said I circled the hypothalamus and said sleep Control Center and of course that's that's pretty simplistic um but it's it makes a lot of sense based on what we've been talking about with nram and wake that there's these these really important control centers for for putting us to sleep or waking us up keeping us awake keeping us asleep but when it comes to REM it seems like the uh the the actual circuits the the control centers so to speak are not in the hypothalamus but in the brain stem so I am going to use this this brain model here this is the brain sorry this is the brain stem and uh this right here is the the pons and uh the the REM generating circuits and the The Gatekeepers are also uh seem to be in this upper kind of brain stem midbrain ponds region um so that's just to mention that Rems seems to have a little bit different circuitry compared to nram and uh wake Okay so The Gatekeepers the the circuits that keep us from going in to rim while we're awake or when we're in nram sleep the main control center for this is in What's called the ventrilateral periaqueductal gray that's a bunch of syllables and words but basically it's referring to a nuclei that's in the brain stem and it's in the midbrain if you're interested but the the periaqueductal gray is also important for pain and aspects of emotion but in this case what it seems to be doing is um sending inhibitory projections sending these connections that basically shut down the activity of regions that turn on REM and regions that uh wake us up but but importantly they they seem to be stopping the REM generating regions from turning on let's see I'm gonna REM seems to Bruce says REM seems to be a what-if scenario like the brain is throwing information together to explore and build up the prediction error system that's a really cool idea I think I don't know if there's there's direct evidence or not for that but it seems like yeah the the um a dream state may or the the REM State and dreams we have in it maybe that is uh something to do with increasing our um ability to to predict the future and and like you said building up the prediction era system that's a great idea um but anyway uh getting back to this neural circuitry so we've got the periaqueductal gray this this nuclei in the brain stem that's keeping us from going into REM and interestingly the these regions these Gatekeepers um uh this ventral lateral periactal periaqueductal gray is most active when we're awake right most activists keeping us from falling in to REM sleep while we're awake of course it's a little bit less active when we're in nram sleep so you know of course it needs to be active to keep us from going into REM but it's a little bit less active than it is during wake which which kind of makes sense because you only go into REM sleep after you've been in nram and then they're actually this region is totally inactive almost totally inactive during REM sleep so um also in in rodents activating this region suppresses REM sleep while inhibiting it increases the duration of a rem about okay so then we talked so that was the gatekeeper that's keeping us from going into REM sleep when that's inactivated there's there's actually a separate circuit or set of circuits that put us into REM sleep so um it's another uh the kind of control center for these are also in the brain stem but in a region called the pons and protect if you're interested specifically this is uh the sublateral dorsal nucleus of the pons this is the main Rems generating nuclei or nucleus sorry it is uh strongly activated when we're in rem but it's also active when we're awake which is interesting um but stimulating that region increases the duration of a rem's about while inhibiting it can decrease the rem's duration so some some good evidence that it's at least involved in maintaining REM and um there's also just below the ponds in the brain stem another set of nuclei in the medulla uh there's another Rems regulator so basically the big picture that we're seeing here is that REM seems to be controlled mainly by these nuclei these these circuits that um where they're sort of control centers are in the brain stem again there are other regions that are involved in generating REM sleep and maintaining it areas that have to do or um sorry areas like the basal ganglia like we mentioned earlier as well as actually the amygdala and there's um seems to be heightened amygdala activity when we're in rem at least certain parts of REM sleep and there's some scientists who believe that that may have to do with um kind of the emotional content of Dreams maybe the the amygdala is activating and um kind of doing this sort of sleep fight or flight response thing but but that's just one idea it's just mentioning that to say that um there are other regions and even though I said the hypothalamus is not really involved in REM sleep there are certain little nuclei areas of the hypothalamus that also promote REM sleep so I don't want you to um walk away from all this neural circuitry thinking that it's it's super simple that there's just these individual circuits that you click them on and they turn us uh they make us go to sleep we're going to end RAM or REM sleep um the brain as always is a very Dynamic interconnected system and it's going to have kind of multiple overlapping mechanisms for putting us to sleep keeping us in nram transitioning us from each of the stages of nrim I mean we didn't even talk about um nram stage one or stage two or stage three we just talked about it as a whole as um and and so you can imagine you can get uh more and more fine grain with with uh what's going on in the brain so I'm gonna stop there with uh neural circuitry and kind of go into some some interesting consequences some some final thoughts about um some some interesting questions that we can now answer because we understand the neural circuitry of sleep okay so the first question is why is it so hard at least for me and for many other people to fall asleep on an empty stomach if you're really hungry you might notice that it's really hard to fall asleep it's not impossible excuse me I need a little bit more water as you can probably hear okay sorry about that um so why is it so hard to fall asleep when you're hungry on an empty stomach so the main reason or at least one one of the main reasons seems to be that there's this hunger hormone there's this hormone that's um before I get into that Vian says sounds like it's a miracle we even fall asleep at all with this complexity the you know on the one hand I see what you're saying but then on the other hand there are these ideas that um that sleep may actually be the default that that slow wave activity we talked about that may be a default state of how the brain is wired up so um maybe to flip your your uh um your comment on its head maybe it's a miracle that we stay awake with all this complexity um but anyway that's neither here nor there um back to ghrelin so there's this hunger hormone called ghrelin that's released when we're hungry released into our bloodstream gets into our um our brain and that combined with low blood sugar both stimulate those lateral hypothalamic neurons and um that's that's really interesting because like we're talking about those lateral hypothalamic neurons keep us awake they keep our cortex routes they keep our body awake they they keep the activity or they facilitate activity that's related to wake awake state related processing so ghrelin is stimulating that region and um that is so that's just one that's one mechanism that hunger uh can where hunger can keep us awake um there's a little bit more to that but um that's kind of the basic picture and um but it's not impossible to fall asleep on an empty stomach and that may be because it's not necessarily um inhibiting like sleep promoting regions but just activating wake promoting ones okay the second question is why is it so hard to fall asleep when you're stressed out when you're super stressed out you probably it's like almost impossible to fall asleep um the the basic idea is that stress uh like the Wake promoting brain regions stress can activate the locus ceruleus and that's that noradrenaline producing brain region that sends projections throughout the brain but especially to the cortex and the thalamus keeping us awake keeping us in that state um it can also um activate neurons that that release something called corticotropin releasing factor which is involved in the stress response the cortisol hormone response in your body but um that's so that's kind of like now that we understand this neural circuitry you can kind of piece together well why is it hard to fall asleep oh because sleep is kind of activating the locus ceruleus and that can keep your brain or so stress is activating Locus really is and that can keep your brain from falling asleep in that way um and also that corticotropin releasing factor that I just mentioned that also stimulates those lateral hypothalamic neurons and the locus ceruleus neurons so you've got kind of this double whammy that's keeping you awake while you're stressed um let's see uh ghrelin is released as anticipation of hunger even if we are not hungry but if we're habitual of eating all the time it kicks in just like dopamine yeah that's true but um it's also I mean often when you're you're hungry or anticipating hunger but it does it is released I think when you're hungry um yeah okay so uh the last question that I'm going to cover is which Evolved first was it sleep or wake um that seems like a kind of a crazy question because you might think that of course wake of course the awake state would have Evolved first the animals move around that's kind of what defines an animal against like a plant or a fungi so when you think that the Wake State evolved before sleep but some scientists point out that first there's not really great evidence that uh wake that wake actually um Evolved first and there's another idea that like I was talking about that slow wave activity may be the default state of the brain the way that the brain is wired up it may just be that that slow wave synchronous neuronal activity is kind of a default for the brain there's also the fact that neuromodulators like dopamine and noradrenaline like we're talking about are important in maintaining wake and also important in motivated behaviors so there's this idea that maybe wake as well as motivated Behavior co-evolved and finally um like I just said plants and fungi don't move around they don't have a wake State essentially they're just I don't know kind of always asleep they don't even have a nervous system um so why couldn't an early proto-animal do the same thing why couldn't sleep have Evolved first um that's uh so that's just some some thoughts about that sleep maybe it's so important maybe we need it so badly because it's built in it maybe it Evolved first and then animals awakened um there's there's a lot of ideas about the evolution of sleep the origins of sleep so I'm not going to say that definitively that that's true but just an intriguing idea okay all right so um that's basically it that's all I'm gonna talk about for regarding sleep I really appreciate all the comments and um some corrections on stuff I said I I really do appreciate you guys all being here and um commenting and liking on these videos uh it's it's just like I was saying before we're now 100 independent sense of mind is uh no longer supported by any kind of outside funding and so I I really need your help um like I said if you want contribute to the super chat or the super things eventually I'll have a patreon going I think Taylor got three my co-host on the social brain podcast I think we're gonna have a patreon getting started soon those will be some ways to uh contribute but uh just free ways to support this channel uh you can subscribe like this video post comments and questions and subscribe to the podcast sense of mind on whatever podcast platform you use and maybe give us give it a five star rating as well um so again thank you all so much for being here I I just feel um privileged to be able to do this and I um I look forward to next time let me know in the comments what you want to hear about what kind of topics you want me to cover if you noticed any any mistakes I made or anything um just uh don't hesitate to throw those in there uh really appreciate you guys again um thanks for watching I'll catch you next time