Sleep and Circadian Rhythms Quiz Review Guide

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1. Sleep Patterns in Animals

   1. All animals experience some form of sleep, if we define sleep as a period of quiescence. This is evidence of the deep evolutionary roots of sleep and the biological imperative of sleep, though the reasons for this are not fully understood yet.
   2. Birds and mammals are the only group of animals that experience the characteristic REM/NREM sleep cycles with which we humans are familiar
   3. Amounts of sleep vary widely among mammals, from 2-20 hours per day, as do patterns of the time of day (diurnal, nocturnal, crepuscular)
   4. The complex hemispheric sleep observed in dolphins is also evidence of the biological imperative

2. Biological Rhythms

   1. Ultradian: patterns of behavior or biological cycling that occurs more frequently than once per day. Can you give some examples?

   2. Infradian: patterns of behavior or biological cycling that occurs less frequently than once per day. Can you give some examples?

   3. Circadian: patterns of behavior or biological cycling that occurs approximately once per day.

      1. The internal (endogenous) biological clock is centered in the suprachiasmatic nucleus (SCN) in the hypothalamus.

         1. The SCN sits just superior to the optic chiasm (hence the name) which corresponds to the influence of light cues (see Zeitgebers)

         2. Experimental evidence

         3. Ablation of the SCN in rats results in complete disruption of the sleep/wake cycle

         4. SCN neurons isolated from the rest of the rat brain will continue to experience cycling patterns, but the rest of the brain does not

         5. Humans with damage to the SCN experience significant sleep disorders

         6. The endogenous clock is regulated by a feedback loop inside the cells of the SCN neurons. Two transcription proteins (BMAL1 and Clock) induce DNA transcription of two other proteins (Cry and Per) which in turn inhibit the transcription proteins and break down in approximately 25 hours, thus setting up a feedback loop that cycles in 25 hours

         7. This cycle, when free running, is a little longer than one day, but can be influenced by external cues about the time of day, called Zeitgebers (literal translation from German = “time giver”). The primary Zeitgeber is the light/dark cycle

      2. Dysfunction of the endogenous clock can lead to sleep phase disorders, such as delayed or advanced sleep phase disorders, which drive people to fall asleep before dark or stay awake well past dark

3. Sleep Wave Patterns in Humans

   1. While awake and active, human EEGs show fast (high frequency), asynchronous (low amplitude) waves. These are classified as beta waves or, for slightly more relaxed activity, alpha waves. Wave frequency can be as high as 30 Hz.
   2. During slow wave sleep, (NREM1, 2, and 3) brain waves become increasingly slower, down to approximately 0.5-1 Hz. In addition, amplitude becomes much higher, indicating a synchronization of neurons firing all at once and then not at all.
   3. During REM sleep, brain activity resembles Stage 1 or even wakeful EEGs, though some characteristic patterns such as sawtooth waves distinguish it from other stages.

4. Stages of Sleep

   1. NREM 1: What are the characteristic physiological and neurological changes that occur during this stage?

   2. NREM 2: What are the characteristic physiological and neurological changes that occur during this stage?

   3. NREM 3/4: What are the characteristic physiological and neurological changes that occur during this stage?

   4. REM

      1. Most dreaming occurs during REM sleep

      2. REM sleep is characterized by rapid eye movement under the eyelids, however several unique physiological changes occur during REM

         1. Activation of the visual and somatosensory cortex, hippocampus, and amygdala
         2. Deactivation of the prefrontal cortex (PFC)
         3. Paralysis of spinal cord motor neurons so that the dreamer does not act out motor functions

   5. Typically, humans begin sleep in NREM 1 and sleep deepens (going through NREM 2 and NREM 3/4 over the first 45 minutes of sleep, then gradually return back through the cycles in another 45 minutes. Instead of waking after returning to NREM 1, the person will enter REM sleep briefly before the cycle begins again. This can be charted in a hypnogram.

   6. REM cycles are brief in the first few sleep cycles of the night, and increase in length while periods of deep sleep shorten, this most deep sleep occurs in the first half of sleep and most REM occurs in the second half

5. Neural control of sleep

   1. Two primary circuits in the brain promote wakefulness

      1. When light is present, the SCN excites the lateral hypothalamus (LH) to produce orexin (sometimes called hypocretin) which itself excites several different regions to stimulate the cerebral cortex
      2. Orexinergic neurons in the LH also stimulate the pathways in the pons (PPT) and midbrain (LTN) which project to and excite the thalamus, increasing awareness of sensory inputs
      3. Orexin also projects to the REM-OFF neurons in the midbrain, keeping the REM circuitry off during wakefulness

   2. The ventrolateral preoptic area of the hypothalamus (vlPOA) sends inhibitory projections to all of these regions, shutting them off and promoting sleep.

      1. The vlPOA can be activated by several different signals (or many in combination)

         1. The SCN projects to the pineal gland, inducing the release of melatonin and promoting sleep
         2. Accumulation of adenosine during wakefulness stimulates the vlPOA directly, as the neurons there contain adenosine receptors. (Caffeine is a neuroactive drug that blocks these receptors, at least temporarily)
         3. Satiety signals from the gut (after eating a large amount of food) stimulate the vlPOA (which is why you have the urge to nap after Thanksgiving supper)

   3. Once the vlPOA is activated and orexin is inhibited, the brain enters NREM1. However, since orexin is no longer stimulating the REM-OFF neurons, after some time, these neurons go quiet, and stop inhibiting the REM-ON neurons in the pons. The REM-ON and REM-OFF are mutually inhibitory, so these also flip-flop and only one is active at a time.

   4. REM-ON neurons are excited by the amygdala as well, so when the amygdala is particularly active after an emotional experience, generally the person will experience greater periods of REM sleep that night

6. Sleep deprivation

   1. Sleep is a biological imperative, and deprivation has drastic effects, up to and including death (see fatal familial insomnia)
   2. Most humans can go no more than 4-5 days without sleep, and in that time will experience lack of coordination, disorientation, impaired immune function, and irritability
   3. People who are deprived of sleep will sleep more than usual as soon as they are able (sleep debt), and people who are deprived of REM sleep in particular will spend more time in REM the following night.

7. Purpose of sleep

   1. Emotion processing: the amygdala is overactive during and after an emotional trauma. After REM sleep, the amygdala activation in response to memories of that emotional trauma are reduced.
   2. Developing children sleep more, and experience more REM sleep when they do, suggesting the role of REM sleep in brain development such as synapse formation
   3. Memory consolidation occurs during sleep, with non-declarative memory most improved during REM and declarative memory most improved during NREM

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