Lecture 19: Sleep Flashcards
Why do we sleep
Evolutionary adaptation - inactivity theory and energy conservation.
Cleaning of the brain - lymphatic system disposes of metabolites (“waste”); glial cells/astrocytes can take up metabolites during sleep.
Memory processing - promotion of newly formed memories, consolidation/memory retention.
Developmental plasticity - more sleep in neonates.
Sleep over the course of our lifetime
The amount of sleep we get declines steadily over our lifetimes after conception/birth.
Rhythmicity of sleep
There seems to be a rhythmicity to sleep, which we observe in different physiological metrics.
On average, we get about 7 hours of sleep +/- 1 or 2 hours.
Circadian rhythmicity
Seeing oscillatory activity; sleep and circadian rhythm controls hormones, neuromodulators, body temperature.
Body temp is higher when awake, lowers during sleep, goes back up when awake.
Growth hormone levels are low during the day, stay up in early stages of sleep, fall back down in later stages of sleep and stay down during the day.
Cortisol gets recharged during sleep.
What is responsible for signalling circadian light changes?
Photoreceptors.
What are the important nuclei in regulating the sleep-wake cycle?
Paraventrical nucleus, lateral hypothalamic area, tubero-mammilary nucleus, suprachiasmatic nucleus.
Suprachiasmatic nucleus SCN
Very important for sleep because many of its neurons have pathway expressing clock genes.
What is the molecular feedback loop believed to govern circadian clocks in mammals?
2 important proteins: BMAL1 and CLOCK.
- Light-dependent transcription of Clk and Bmal1 genes.
- B and C proteins are synthesised and associate as dimers.
- C-B dimers bind to E-boxes and act as TFs - re-entering the nucleus and helping transcription of other proteins.
- Synthesis and modification of temporally regulated proteins; which re-enter the nucleus and inhibit Bmal1 and Clk ==> negative feedback loop.
Clk abd Bmal1 oscilalte over 24 hours. They have periodicity => degradation of Clk or Bmal1.
Circadian rhythmicity in the absence of light
Light sets the 24 hour rhythm. Going without light causes the rhythm to drift a little. Because of the proteins in the SCN (Clk and Bmal1), there is still a rhythm even in the absence of light.
The fact that the rhythm of the circadian rhythm drifts a bit in the absence of light suggests input into the retina for the SCN.
How photoreceptors are responsible signalling circadian light changes
Via ganglion cells, which are in the deep layers of the retina. Ganglion cells mostly hubs; but some are photoreceptors.
Photosensitive retinal ganglion cells synapse directly onto SCN = setting periodicity based on light.
Important nuclei in regulation of sleep-wake cycle => hypothalamus and brainstem nuclei connectivity
Inputs from the retina; proteins in SCN setting rhythm. Output to brainstem. There are neuromodulator receptors in the brainstem; the hypothalamic nuclei can affect the brainstem nuclei, which gives the SCN direct control of the entire brain.
How widespread are the neuromodulator systems in the brain?
Very. In this rhythmicity, up or down regulation of neuromodulators. Cocktails that can lead to sleep. SCN can spread neuromodulators around the entire brain.
What do these neuromodulators do?
Depending on levels of neuromodulators, they can lead to changes in activity of neurons. Clock genes in the hypothalamus, biased by ganglion cells = SCN has direct control over neuromodulators which leads to changes in the brain.
Thalamic neurons during the sleep cycle
When asleep, they are hyperpolarised => slow wave activity. When awake, activation of brain state nuclei, resulting in losing slow bursting activity.
During slow wave activity, the bursts are more than 1 AP. Simplest form of slow burst activity => slow way sleep; slow oscillatory activity.
Oscilations in slow wave activity are much faster than molecular oscillation of Clk and Bmal1. Whether they are up or down leads to these oscillations.
Why are Clk genes oscillatory
Because of the negative feedback loop.
Irregular vs synchronised activity
Electroencephalography.
The neurmodulator environment changes the firing activity.
Irregular = some activity; low amplitude, desynchronised activity. High frequency activity.
Synchronised = whole system set to oscillation; synchronised slow activity. High amplitude, low frequency. EEG sum has lower frequency but higher amplitude vs the EEG sum of irregular activity during wake. See this when asleep or not focused on anything.
Synchronised activity occurs when the majority of populations of neurons firing at the same time => averaging => high amplitude.
Difference in brain waves of sleep and wakefulness
We can see clear differences in EEGs between wakefulness and the different stages of sleep.
Wakefulness - low amp, high frequency waves.
Stage 1 - low amp, high frequency waves, but less so than when awake.
Stage 2 - also low amp, high frequency, but with sleep spindles that are higher amplitude and with K-complex waves.
Stage 3 - slow wave sleep, which is high amp and low frequency waves.
What happens if you stimulate a cat’s reticular activating system
Wake the cat up, as if you touched it.
What happens if you stimulate the thalamus
Stimulate slow wave activity => induce sleep. Stimulating thalamic cortical sloop which therefore induces sleep.
What have EEG recordings during the first hour of sleep in humans shown us?
There are many different stages of sleep; higher brain wave activity during REM sleep. Similarities in brain wave activity means we also have to look at muscle activity to determine sleep stage.
Proportion of different sleep stages throughout the night
The duration of REM sleep increases from 10 minutes in the first cycle to up to 50 minutes in the final cycle; note that slow-wave (stage IV) sleep
is attained only in the first two cycles.
Physiological changes during the various sleep states
Electrical activity and other physiological characteristics between REm and wake are similar. Eye movement = random.
