[SOUND]. Welcome back to Medical Neuroscience and welcome back to my home. It's a lovely evening, as the sun is setting. It brings to mind our topic for today and that is Thinking About Transitions in sleep and wakefulness. Transitions of brain and body that are tied to our daily rhythms. So, today's session is going to relate to a couple of our key core concepts in the field of neuroscience. Namely, that neurons communicate using both electrical and chemical signals. We haven't quite given up yet on this core concept. It continues to obviously be foundational for everything we're learning about how the brain works, and today we're going to focus in on a set of neurotransmitter systems that are especially important. In transitions in brain state. We're going to be talking about circuitry in the brain that is really remarkably conserved, even down to some of the molecular details as to how this circuitry operates. So, we're going to be talking about circuitry that's genetically determined and is foundational for the function of the nervous system. And I hope you'll appreciate that the fundamental discoveries of these kinds of systems in the brain that can modulate brain state, sleepiness, wakefulness. these are very important concepts that are essential for understanding how to best promote health and wellness. So these kinds of fundamental discoveries are what will promote healthy living and the treatment of disease, and I think as many of us can, relate to rather easily, disorders of sleep. And disorders of, being able to, optimize one's vigilance, one's attention throughout the day. these are huge issues. And those that require a deeper understanding of the brain mechanisms involved. This topic has several learning objectives that I'd like for you to take away from this tutorial. I'd like for you to be able to discuss the concept of circadian rhythms. And provide some examples of homeostatic functions and overt behaviors that are modulated on a circadian or a daily rhythm. I would like for you to be able to discuss the underlying neural systems that account for circadian rhythmicity in body and brain. I'd like for you to be able to describe the basis of, of brain waves. That is, the rhythms in the brain that can be detected from the surface of the scalp via means of electroencephalography. And I'd like for you to be able to use these methods to characterize. The stages of sleep, and these will include stages that we call non-R E M, or non-REM, sleep as well as R E M, or REM sleep, and lastly I want you to be able to describe the functional states of thalamocortical projection neurons. These are the neurons that project from the thalamus to the cortex. And I want you to appreciate how their state can change. And, that this change in state can be used to understand the transitions from wakefulness to non-REM sleep, to REM sleep and back up through stages of sleep towards wakefulness once again. Well, I'm going to do things just a little bit differently in this tutorial. I don't have study questions for you at the end. Rather I just want to seed our discussion with a few questions right at the beginning. I'm just going to talk you through these. They will require a yes or a no answer or perhaps a maybe of an answer. But I'm not going to implement this. On the website, so they'll be nothing for you to click, I just want you to think and respond, when I prompt you to do so. Okay, so we've got some questions about sleep that, hopefully will set the stage for the remaining time that we have together in this tutorial. Okay, so here's the first question. Well, really a statement. But we'll think about it as a question. Having a good night's sleep is essential for good health. What do you think, yes or no? I, I hope we all agree that the answer is a definite yes. A good night's sleep is essential for good health. Prolonged sleep deprivation can be lethal. Well, indeed this is the case. We know this from animal studies, and unfortunately some instances of. human torture where we suspect that, part of the consequence of the mistreatment has been the impact of chronic sleep deprivation. Okay we're going to talk some about dreams today. So what do you think, having dreams during sleep is essential for good health. Well, this one I'd have to say is a maybe. I think that, dreams, are adaptive and they certainly are pervasive, throughout not just, humans but also non-human mammals seem to have. Something like dreams, and therefore we imagine that they must be adaptive, since they're throughout our mammalian phylogenetic lineage. However, there are individuals who because of either dysfunction, or because of medication. Are not able to dream, and these individuals seem to get along pretty well. I think, if you were to ask them, they might say, well, their health could be better, but perhaps they have no major complaints. So this remains a bit of an open question, whether having dreams during sleep is essential for good health. But hopefully research will help address that. as we go forward. Okay, have another question for you about dreams. Some people dream regularly, others don't dream regularly, and some people never dream at all. I suppose I'm talking now about people that don't have a disease or dysfunction. Of their brain state system. Nor am I talking about individuals that are on medications that are interfering with their capacity to dream. So with those two caveats stated, what do you think? Are there people out there who, who don't dream? Now I've got members of my own family who have told me. More than once that they just don't dream, or it's been months since they've dreamt. So what do you think? What's going on there? Well, I think we're going to answer that as we get further along in this tutorial, but I suppose what I would say is that. These folks are dreaming, even though they are not remembering their dream. And that's probably a good thing, that's probably a healthy indication of a good night's sleep. Okay, I've got some more questions for you. Sleep is a time when the brain and the body shut down. For rest and relaxation. Well, since I wrote these questions, I know that, there's, a bit of extremism going on here. shut down is really too harsh a phrase. that sort of gives away, the answer, perhaps. what we're going to discover is that the body and the brain they do rest and relax. And we think that there is an important restorative function to sleep, however, the brain is far from shut down and certainly the body is not completely shut down, otherwise we wouldn't survive. the, the nights sleep. but there are some fascinating changes in body state, that accompany changes in brain state. And we do want to talk about that for both REM sleep and non-REM sleep. All right, well I suppose I'm giving you sort of a lecture. Even though you're free to stop and start this at any time. But, suppose you happen to be one of those people that doze off during lecture. I've got, quite a few of them in my classes here on campus. So I know of which I'm speaking. If you are that person, do you think you might need more sleep at night? Yeah, I'd say you do. I think maybe a question is, might you even have a disorder of your sleep that requires some kind of intervention. We're going to talk about sleep disorders near the end of today's tutorial. All right, one last question. If you snore loudly at night and are excessively sleepy during the day. Might you have a sleep disorder? Maybe you know some of those folks. Maybe some of those go to classes with you and are sitting next to you in lecture and snoring away. indeed, these folks they, they just might have a sleep disorder, and someone needs to get into their life a little bit and figure out what's going on. because we shouldn't consider it to be normal for people to be falling asleep and snoring excessively during the day. Okay, well hope those questions got you in the frame of mind, perhaps the state of body and brain, to think together with me about this topic. So let's move on, and begin to consider some various aspects of sleep. Okay well I think we're ready to move on and we'll talk about some of the parameters of sleep and then begin to dive into some of the mechanisms. And as we get there I do have one more question for you. And that is, how much sleep is enough? Well this is a distribution of sleep. time for a large cohort of individuals. So, I think these data are fairly reliable, they seem to be fairly consistent across human cultures and across time and it seems as though what we require is somewhere in the order of 7.5 hours of sleep. But of course, this is just population data. And I wonder where might you be on this curve? might you be right here at the mode of this distribution? perhaps you're here on the rightward tail. Well, if you're like me, and I suspect that you are you may find yourself over here somewhere. And hopefully moving in the upward direction. And not slipping further down to the far left. But in any event I think the answer to the question, how much sleep is enough? Is answered by that duration of time that allows you to rise in the morning feeling refreshed. And ready for the work that you have that day. And that answer, how much sleep is enough, very well may be a larger number than what characterizes your life right now. So, maybe you and I together can agree that we're going to work on this, and try to more optimize the amount of sleep that we get on a daily basis. Well it turns out a part of the answer to that question may depend upon where you are across the age and stage of life. And here are data that plot the normal amount of sleep from a fetus on through embryonic life. Into the post natal period and all the way through older adulthood. And what we see is that, just in utero we find that our embyronic forms require the greatest amount of sleep. So here is a fetus into the last third of, gestation and, we see that they're sleeping almost all the time. and this can be measured in various ways, and, we'll talk about some of those ways in just a little while. But as that third trimester begins to roll towards full term, we see that there is a decrease in the amount of sleep. That's required. And it continues to diminish throughout the early years of life. So you'll notice this gradual decline in the amount of sleep that people experience throughout life. And note in particular how it trails off through our older adult years. This is often a, a problem for older adults who. want to have more of the sleep that they experienced when they were in their younger years. And changes in brain and body simply are not facilitating the regular duration and depth and quality of sleep that they may have had when they were younger. So that's one of the many accommodations to. Growing older that we face as we age. So, this sort of begs the question then, and the question would be then, why do we sleep? Is sleep essential? Well, we know that sleep is essential from. experimental studies such as this. And this is really quite a devious experiment. And I'll just take you through this. so there are two laboratory mice. that are connected with a means to record their brain waves. we'll talk a lot more about that as we get further into this. And these mice are held within a chamber that's sitting on top of a turn table. Now this turn table is triggered by high amplitued brain waves that are recorded from the experimental animal. And the experimental animal. Is this guy back here, this this white mouse. And so whenever this mouse starts to fall asleep we'll describe this in a little bit, there's a marked increase in the amplitude of this animal's brainwaves. Well once these brainwaves hit some trigger point. They turn on a motor that causes this stage to rotate. And so what this means is that this experimental animal basically is being agitated whenever it tries to fall asleep. Now this this brown mouse over here. this animal can sleep while the white mouse is active and otherwise awake. So this brown mouse, even though he's confined within a small compartment, is going to do just fine. But the white mouse, on the other hand, is in for real trouble. So this is what has happened now. To this white mouse over time. We see that after a couple of weeks of sleep deprivation, things really begin to change rather dramatically for this animal. We see that despite a steady increase in food consumption, going out about three weeks of sleep deprivation. Body weight is, really, collapsing on this animal. So this is just an indication that there is just widespread organ failure. And after several weeks of this experiment this animal will die. Unless it's given an opportunity to acquire sleep. Now, you may be wondering about human beings, and I, I think in your textbook, you can read about what is, essentially, the longest known voluntary period of time where an individual has been deprived of sleep. And, this went on for many, many days and the individual then, tried to catch up following the conclusion of the experiment and, seemed to be okay, in the end. But I suspect that there may have been some. At least short term, if not long term consequences to this extended period of voluntary sleep deprivation. So the answer to the question, is sleep essential? Absolutely. Sleep is essential for life. But why do we sleep? Well, we're going to try to answer that at least partially as we go. I suppose I can just tell you up front, the short answer is that nobody really knows why we sleep. there's general consensus that there's a kind of restorative function that takes place when we sleep. And there's even some speculation that it might actually be a conservative mechanism that is associated with endothermy or warm bloodedness. that allows our cells to retain a reserve in the form of chemical energy in the currency of Adenosine Triphosphate, ATP. But these ideas are still really unproven. And there's a lot of deep thought, both scientific and, and philosophical. that has gone into addressing this question as to why do we sleep. And we don't yet quite have a definitive answer.