Sleep and Circadian Rhythms

• The presentation provides an overview of sleep and circadian rhythms.
• It focuses on biological rhythms, neural systems, and sleep stages.

Learning Objectives

• Biological rhythms and the role of environmental cues on circadian rhythms are defined.
• Explains the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in circadian rhythms.
• Details the stages of sleep and how sleep patterns change over time.
• Discusses the biological functions of sleep and the neural systems that underlie sleep.

Biological Rhythms

• Circadian rhythms are functions of a living organism that display a rhythm of approximately 24 hours.
• Nearly all physiological, biochemical, and behavioral processes exhibit circadian rhythmicity.
• Diurnal animals are active during the light, like humans.
• Nocturnal animals are active during the dark, such as rodents.
• Infradian rhythms occur less than once a day, such as the menstrual cycle (~28 days), seasonal body weight changes, and breeding seasons.
• Ultradian rhythms occur more than once a day, including bouts of activity, feeding, and hormone release.

Circadian Rhythms in Rodents

• Rodents display extraordinary precision in their running wheel activity.
• This regularity is thought to reflect a biological clock.

Endogenous Clock

• Circadian rhythms are generated by an endogenous clock.
• An animal's circadian rhythm is typically set by light.
• A zeitgeber is a cue used to synchronize with the environment.
• A phase shift is a shift in activity in response to a synchronizing stimulus, like light.
• Entrainment is the process of shifting the rhythm.
• Entrainment synchronizes internal rhythms with the environment.
• A free-running animal maintains its own cycle without external cues.
• The period, or time between successive cycles, may not be exactly 24 hours.

Circadian Rhythms in Humans

• Sleep is synchronized to external events, including light and dark.
• Stimuli such as artificial lights, food, jobs, and alarm clocks entrain humans to be awake or asleep.
• Humans have a free-running period of about 25 hours in the absence of cues.

Hypothalamus and SCN

• Large lesions of the hypothalamus interfere with circadian rhythms.
• The biological clock is located in the suprachiasmatic nucleus (SCN), situated above the optic chiasm in the hypothalamus.
• Lesions of the SCN do not alter sleep or activity time but abolish circadian periodicity.

SCN Transplants

• Normal hamsters have free-run activity longer than 24 hours and mutant hamsters (tau gene) have free-run activity around 20 hours.
• Transplanting SCN tissue from mutant hamsters into non-mutant hamsters with SCN lesions restores circadian rhythms, matching the donor's shorter period in a constant light environment.
• Reciprocal transplants yield similar results.

Neural Mechanisms of Entrainment

• Cutting optic nerves before the optic chiasm disrupts light-dark cycle entrainment of circadian rhythms.
• Cutting optic nerves after the optic chiasm does not have the same effect.
• Fibers of the retinohypothalamic tracts leave the optic chiasm and project to the adjacent SCN.
• Retinal ganglion cells that project to the SCN form the retinohypothalamic pathway.
• These ganglion cells do not depend on rods and cones.
• Most of these cells contain melanopsin, a photopigment making them sensitive to light.

SCN Proteins

• SCN cells in mammals produce two proteins: Clock and Cycle (Bmal1 in mammals, Cycle in Drosophila).
• The Clock/Cycle dimer promotes transcription of two genes: Period (per) and Cryptochrome (cry).
• The Per/Cry protein complex enters the nucleus and inhibits the transcription of per and cry genes.
• Per and Cry protein degradation lifts the inhibition, restarting the cycle.
• The entire cycle takes 24 hours, driving SCN activity.
• Retinal ganglion cells detect light and release glutamate in the SCN.
• Glutamate triggers events promoting Per protein production, shifting the animal's clock and behavior.
• Concentrations of Per and Cry mRNA and protein change over the course of the day.

Stages of Sleep

• Stage 1: EEG is similar to awake but slower, with low-amplitude, high-frequency waves.
• Stage 2: Characterized by:
  • Sleep spindles, which are bursts of 12–14 Hz waves.
  • K complexes, one large negative (upward deflection) wave followed by one large positive wave.
• Stage 3: Features delta waves, which are large and slow.
• The sleeper progresses to stage 3 sleep and then returns to stage 2 and emergent stage 1.
• Emergent stage 1 differs from initial stage 1, featuring:
  • Rapid eye movements (REMs).
  • Loss of body core muscle tone.
• Sleepers cycle through these stages in 90-minute intervals.
• Durations of emergent stage 1 periods lengthen as the night progresses.
• Emergent stage 1 sleep is REM sleep, while other stages are non-REM (NREM) sleep.
• Stage 3 is slow-wave sleep (SWS).
• During REM sleep, there are REMs, a loss of core muscle tone, low-amplitude/high-frequency EEG, increased cerebral and autonomic activity, and possible muscle twitches along with penile erection.

Lifespan and Sleep

• Mammals generally sleep more during infancy compared to adulthood.
• Infant sleep is characterized by 50% more REM sleep, which may provide essential stimulation to the developing nervous system.
• By adulthood, an average of about 8 hours of sleep is reached including which 20% is REM sleep.
• Infants take several weeks to show a regular sleeping and waking cycle.
• A 24-hour rhythm is only evident by 16 weeks which can be a brain development reflection
• REM sleep in infants is quite active with smiles, vocalizations and twitching.
• At puberty, most people will shift their circadian rhythm of sleep by 2-3 hours so that they get up later in the day.
• Sleep delay shifts are hypothesized to occur based on the influence of pubertal-related hormones.
• Total time asleep declines and the number of awakenings increase with age.
• The most dramatic decline is the loss of time spent in stage 3.
• At age 60, one spends only half as much time in stage 3 as at age 20 and by age 90, stage 3 disappears.

Biological Functions of Sleep

• Energy Conservation: Includes reduced blood pressure, respiration rate, heart rate, and temperature.
• Body Restoration: Sleep restores the body by replenishing metabolic requirements, such as proteins; most growth hormone (GH) is released during SWS.
• Memory Consolidation: Sleep aids in consolidating memories of events experienced before sleep and may reduce interfering stimuli.

Neural Systems of Sleep

• Learned tasks neural activity patterns re-created during wakefulness.
• Transection experiments indicate different sleep systems originate in different brain parts.
• Isolated brain (encéphale isolé) involves an incision between the medulla and spinal cord.
• Animals show signs of sleep and wakefulness, meaning networks reside in the brain.
• Isolated forebrain (cerveau isolé) occurs by an incision in the midbrain.
• The forebrain generates constant SWS but not REM when Electrical activity is shown.
• Basal forebrain generated constant SWS activity
• Neurons in the region become active at sleep and will release GABA.
• Activity in the nearby tuberomamillary nucleus is suppressed by GABA.
• The reticular formation enables the cortex to be activated.
• Electrical stimulation of this area will wake animals up.
• Forebrain and reticular formation guide the brain between SWS and wakefulness.
• An area near the locus coeruleus in the pons, is responsible for REM sleep.
• Some neurons in this region will only activate during REM sleep.
• Inhibition of motor neurons is caused to keep them from firing and disabling the motor system during REM sleep.
• Small locus coeruleus ventral lesions and prevent muscle tone loss during REM sleep.
• Hypocretin neurons or orexin neurons in the hypothalamus, project to other sleep system centers.
• Axons travel to the tuberomamillary nucleus inhibited by the basal forebrain to induce slow waves sleep (SWS).
• A hypocretin-based sleep center that controls whether you are awake, in SWS sleep, or in REM sleep.