00:03Sleep is an essential biological process, and although it may seem like a state of inactivity,
00:08it involves highly organized changes in brain activity that follow predictable patterns
00:13throughout the night.
00:15These patterns are best observed using polysomnography, which combines electroencephalography to measure
00:20brain activity, electromyography to measure muscle tone, and electrooculography to measure
00:26eye movements.
00:27Using the results from these types of recordings, researchers have divided sleep into two major
00:32types, non-rapid eye movement sleep and rapid eye movement sleep, or REM sleep.
00:39Non-REM sleep can be subdivided into three stages.
00:43Stage 1 involves the transition from wakefulness to sleep.
00:47When someone is awake, an electroencephalogram, or EEG, will typically record high-frequency,
00:53low-amplitude brain waves.
00:55When someone begins to fall asleep, they enter stage 1, during which an EEG records low-amplitude
01:01waves of mixed frequencies.
01:04People are typically easily awakened from stage 1 sleep, and it is a relatively short stage
01:08of sleep overall.
01:11Stage 2 sleep is characterized by the presence of phenomena on an EEG known as sleep spindles
01:16and K-complexes.
01:18Sleep spindles are trains of high-frequency waves.
01:21A K-complex involves a biphasic wave that stands out from the rest of the EEG.
01:27Stage 3 sleep is also known as slow-wave sleep or deep sleep.
01:32In stage 3, delta waves, which are low-frequency, high-amplitude waves, make up a significant proportion
01:39of brain activity.
01:42REM sleep differs in several key ways from non-REM sleep.
01:46The EEG during REM sleep resembles wakefulness, but muscle tone is profoundly reduced due to
01:52the inhibition of motor neurons by brainstem circuits.
01:55This inhibition of motor neurons prevents us from acting out our dreams, which are typically
02:00most vivid during REM sleep.
02:02Of course, REM sleep is also associated with the rapid eye movements that occur in this
02:06stage.
02:08Throughout the night, a person cycles through these stages of sleep usually around 4 or
02:135 times, with each cycle lasting about 90 to 110 minutes.
02:18The transition between sleep and wakefulness is controlled by a balance of arousal-promoting
02:23and sleep-promoting systems in the brain.
02:25Wakefulness is supported by widespread ascending arousal networks, which include but are not
02:31limited to acetylcholine neurons in the pedunculopontine and laterodorsal tegmental nuclei, norepinephrine
02:39neurons in the locus coeruleus, serotonin neurons in the raphe nuclei, and histamine neurons in
02:46the tuberomammillary nucleus.
02:48The tuberomammillary nucleus is activated by neurons in the hypothalamus that release orexin,
02:54also known as hypocretin.
02:57Antihistamines inhibit the histamine neurons in the tuberomammillary nucleus, which is why
03:01they can cause drowsiness in some people.
03:04While these areas are thought to play a role in wakefulness, research suggests there are
03:09other regions and neurotransmitters, including glutamate, GABA, and others, that are crucially
03:14important, and understanding arousal-promoting areas in the brain is an area of active research.
03:21The transition to sleep is thought to be controlled to a large degree by the inhibition of these
03:25ascending arousal systems.
03:27For example, neurons in a nucleus of the hypothalamus called the ventrolateral pre-optic nucleus,
03:33or VLPO, project to most parts of the ascending arousal system and release the inhibitory neurotransmitters,
03:40GABA and galanin, onto these wake-promoting regions.
03:44Neurons in regions like the VLPO are also inhibited by neurons in the arousal system,
03:49which creates an arrangement sometimes referred to as a flip-flop switch, where each system
03:54turns the other off when it is active.
03:56This allows for rapid transitions between sleep and waking states.
04:02The generation of non-REM and REM sleep also involves distinct patterns of neural activity.
04:08During non-REM sleep, neurons in the thalamus fire in a synchronized pattern with neurons
04:13in the cortex.
04:14It is thought that this activity might reduce the transmission of sensory signals, in effect
04:19disconnecting the cortex from the outside world.
04:22During REM sleep, however, certain neurons in the pons drive activation of the cortex,
04:27while others project to the medulla and spinal cord to inhibit motor neurons and cause the
04:32paralysis characteristic of REM sleep.
04:36While these systems help to regulate transitions between wake and sleep, and vice versa, other
04:41homeostatic and circadian factors regulate when we feel tired or more alert.
04:46One important factor in producing the desire for sleep that increases the longer we stay
04:50awake, often called sleep pressure, is a neuromodulator called adenosine.
04:56During periods of wakefulness, the cells of the brain use ATP for energy, and in the process
05:01ATP is converted to a byproduct called adenosine.
05:05Thus, the longer someone is awake, the more adenosine accumulates in the brain.
05:10Among its many actions in the brain, adenosine binds to inhibitory receptors that are found in
05:15wake-promoting areas of the brain, in the process causing sleepiness.
05:20Interestingly, caffeine blocks adenosine receptors, which is thought to be how it
05:24achieves its wake-promoting effects.
05:28Sleep timing is further regulated by circadian rhythms, which are 24-hour cycles that regulate
05:33a long list of physiological parameters.
05:36Circadian rhythms act both to counteract sleep pressure during the day and promote sleep at night.
05:42Circadian rhythms are largely driven by neurons in a region of the hypothalamus called the
05:47suprachiasmatic nucleus.
05:49Neurons in the suprachiasmatic nucleus keep time, using rhythmic patterns of gene expression
05:54that repeat roughly every 24 hours.
05:57To ensure these circadian clocks are in tune with the outside world, the suprachiasmatic
06:01nucleus receives information from the retina about light in the environment from a pathway
06:06called the retinohypothalamic tract.
06:09Through this pathway, light serves as the primary external cue for synchronizing the suprachiasmatic
06:14nucleus with the environment.
06:16Activity in the suprachiasmatic nucleus ultimately regulates the timing of a long list of functions
06:21associated with sleep, including body temperature, hormone secretion, and blood pressure.
06:29Neurons in the suprachiasmatic nucleus also help to regulate the release of melatonin,
06:33a hormone that promotes sleep and is released primarily in darkness.
06:38Melatonin is produced in a region of the brain called the pineal gland and also plays important
06:42roles in regulating circadian rhythms through actions like lowering body temperature and increasing
06:48tiredness close to bedtime.
06:51Sleep serves many important functions.
06:54Crucially, it is a way for our body to restore materials used during waking.
06:58It also acts as a period where our energy usage is reduced, typically at a time when expending
07:03energy would have been less beneficial for ancient humans due to our susceptibility to predators
07:08at night and poorer night vision for hunting and gathering.
07:12Sleep also seems to be important in the consolidation of new long-term memories of experiences and information
07:18someone was exposed to during the day.
07:21Another important function of sleep might be the clearance of metabolic waste from the brain
07:25through a network of cerebrospinal fluid-carrying channels called the glymphatic system.
07:29During sleep, the flow of cerebrospinal fluid through these channels increases,
07:34carrying waste products, such as the beta-amyloid proteins linked to Alzheimer's disease, out of the brain.
07:41There are many different disorders of sleep.
07:43A full examination of them is beyond the scope of this video.
07:46Insomnia, which involves difficulty falling asleep or staying asleep, affects a relatively large proportion of people
07:52at some point in their lives.
07:54Sleep apnea, a disorder in which breathing during sleep can be frequently interrupted, is also a common sleep disorder.
08:00And other conditions like restless leg syndrome, narcolepsy, REM behavior disorder, and more,
08:05also involve disruptions to the mechanisms that govern sleep.
08:10and certainly in the consultations of the body of the brain of the brain of the brain of the brain,
