Sleep-Waking and Circadian Rhythms

Circadian rhythm is a sleep–wake cycle/rhythm that repeats every 24 hours.
- It is controlled by:
  - The endogenous (biological) 24-hour clock.
  - Environmental cues called zeitgebers.
- Zeitgeber: An environmental event (like light or dark) that sets or resets a biological clock.

Biological Clock Reset

The biological clock is reset each morning by environmental cues, or zeitgebers.
Periods of sleep and wakefulness synchronize to light cues, entraining waking to occur around the same time each day.
Nocturnal animals' activity is entrained to light cues, becoming active when lights go off.
Without light cues, activity depends only on the biological clock and the animal's activity becomes free-running.
As days get shorter, people may wake and sleep earlier.

Rachel Estrella's Research

Graduate student in Neurobiology and Behavior.
Interested in the role of color in circadian entrainment in Drosophila (fruit flies).
Fruit flies may use color changes as time-giving cues for entrainment, as color changes reliably throughout the day.
Experimental Approach to understand how color is used in the circadian system:
- Live Calcium Imaging: Imaging the neural responses of photoreceptors and clock neurons to different color combinations.
- Behavioral Experiments: Using activity monitors to track fly locomotor rhythms and see how different colors impact entrainment.

Suprachiasmatic Nucleus (SCN)

The suprachiasmatic nucleus (SCN) of the hypothalamus controls circadian rhythms.
The optic tract carries information from the retina to three key brain regions:
- Lateral geniculate nucleus (LGN) of the thalamus (sends visual information to the primary visual cortex).
- Superior colliculus (in the midbrain) is critical for shifting the gaze toward significant visual stimuli.
- Suprachiasmatic nucleus (SCN) of the hypothalamus (body’s internal clock - light means time to wake up).
The SCN lies just above the optic chiasm and detects light and synchronizes daily biological and behavioral rhythms.
Lesions of the SCN in rats (nocturnal) results in behavior that is no longer entrained to the light-dark cycle and behavior occurs at random times.

Melatonin

Melatonin is produced in the pineal gland when the eyes do not receive light, leading to tiredness.
When eyes receive light, the SCN inhibits melatonin production, helping to maintain wakefulness.
Melatonin helps control the body's sleep cycle.
Melatonin levels change with age:
- Infants' melatonin levels become regular at ~3 months (highest levels ~12-8am).
- In teen years, nightly melatonin release is delayed, leading to later sleeping and waking.
- With age, melatonin production decreases, leading to less sleep.
Lack of sleep is associated with weight gain through the inhibitory effect of melatonin on leptin, which signals satiety. Sleep deprivation reduces leptin levels.

Factors Influencing the Sleep-Wake Cycle

Two factors influence the sleep-wake cycle:
- Circadian factor: the biological clock cycles about every 24 hours which needs zeitebers to help the process.
- Homeostatic factor: the longer you’ve been without sleep, the more the body needs to ‘catch up’ on sleep.

Scenarios Illustrating Sleep-Wake Factors

At 3:00 am, feeling tired is due to:
- A circadian factor: the biological clock indicating it's the sleeping phase.
- A homeostatic factor: many hours without sleep.
Remaining awake until 9:00 am may lead to feeling less tired because:
- The homeostatic need for sleep increases, but the biological clock signals the waking phase.
- The biological clock overrides the homeostatic drive to sleep, leading to increased alertness.

Measuring Sleep

Electroencephalogram (EEG):
- Electrodes on the scalp record brain electrical activity.
- Synchronized EEG (sleepy) vs. desynchronized EEG (alert).
- Brain waves reflect summed electrical currents (EPSPs and IPSPs).
  - EPSP - excitatory postsynaptic potential
  - IPSP - inhibitory postsynaptic potential
Electrooculogram (EOG):
- Records eye movement.
- Flat when eyes are not moving; increases during REM sleep.
Electromyogram (EMG):
- Records action potentials on muscle fibers.
- Shows progressively decreasing tone from wakefulness through stages I to IV of NREM sleep.
- Flat in REM sleep.

EEG Activity

Synchronized EEG:
- Occurs when neurons fire in synchrony, generating high amplitude, low frequency waves.
Desynchronized EEG:
- Occurs when neurons fire out of sync, generating low amplitude, high frequency waves.
During wakefulness, EEG shows low amplitude and high frequency (Beta and Alpha waves).
During drowsiness and deeper stages of sleep, EEG waves become higher in amplitude and lower in frequency (Delta waves/slow-wave sleep).
During rapid eye movement (REM) sleep, EEG is of low amplitude and high frequency, resembling EEG while awake and alert.

Sleep Cycles

REM episodes recur about every 90 minutes, growing longer as the night progresses.
During REM, eyes twitch, but large muscles lose tone (muscle atonia), as if paralyzed.
EMG is flat during REM.
Sleepwalking is most likely to occur during non-REM sleep.

Sleep Variation

Sleep varies with age and species.
During early months after conception, the fetus spends all its time in REM sleep (significant metabolic activity with brain development).
Newborn (age “0”) spends ~ 16 hours sleeping, with over half of this time in REM sleep.
Over the years, we spend more of our daily hours awake and less time in REM sleep.
Amount of time spent sleeping ranges from nearly 20 hours per day in the bat to less than 3 hours in the horse.
Large animals generally sleep less than small ones, and small ones rapidly cycle between non-REM and REM sleep (8 min).
Large animals genuinely have low metabolic activity, expend less energy, so have less need for sleep.

Dolphin Sleep

The dolphin sleeps one hemisphere at a time.
One hemisphere of the brain enters slow-wave sleep while the other stays awake to allow the animal to navigate.
There is no evidence of REM sleep in aquatic mammals.

Fly Sleep

In an environment of 12 hours of light and 12 hours of dark, flies are active mostly in the period of light (diurnal).
When vibration is applied to a tube during active (light) hours, flies respond by buzzing around.
During rest (dark) hours, flies are unresponsive unless the vibration is very strong.
If kept awake during the rest period, they show increased rest during light hours (homeostatically regulated).
Caffeinated flies remain active longer.

Brain Mechanisms: Thalamus

The thalamus plays a key role in waking.
The thalamus has excitatory projections to the entire cerebral cortex.
Electrical stimulation of the thalamus generates wakefulness and cortical arousal, even in minimally conscious individuals.

Neurochemicals and Arousal

Several clusters of neurons are activated during waking called ‘waking-on’ neurons.
These waking-on neurons release neurotransmitters that generate alertness/arousal.
Those in green send projections to the cortex, where they release serotonin, norepinephrine, histamine, or orexin.
Those in blue release acetylcholine to the thalamus, which sends axons to the cortex.
Stimulants enhance activity of these neurotransmitters.

Onset of Sleep

Sleep-on neurons in the preoptic area of the hypothalamus release GABA to turn off the brainstem and hypothalamus waking-on neurons.
Critical factors that activate sleep-on neurons:
- Circadian clock in the SCN.
- Accumulation of adenosine, a chemical in the brain that fuels sleep after long bouts of wakefulness.
Caffeine blocks adenosine receptors to prevent sleep-inducing effects.

Thalamus and Cortex Disconnection

During NonREM sleep, the thalamus sends sensory information to the cortex when awake; sensory information is suppressed during sleep.

Surgical Separation and REM Sleep

Surgical separation of the cat brainstem from the forebrain prevents REM sleep.
If the cut is anterior to the pons, there is no REM sleep.
If the cut is posterior to the pons, REM sleep can be observed, but since medulla neurons inhibit motor neurons, the cat can move during REM sleep.

Dreams

Dreams can occur in all sleep stages, but vivid and emotional dreams mostly occur during REM sleep.
Memories are replayed in nonREM sleep.

Brain Activity During Dreams

Posterior regions of the occipital and parietal cortex are typically active during dreaming (visual nature of dreams).
Prefrontal regions that track logical connections between events in time are mostly inactive, but can be activated if recall having had thoughts or lucid dreams.
ildewith[75]
ormalsize % of the emotions described in dreams are negative (e.g., desire to escape from danger).
Thought to be due to high levels of sympathetic nervous activity (fight/flight) during REM, yet motor “paralysis” prevents acting out the dream.

Sleep Disorders

Insomnia: Inability to sleep, most commonly caused by stress and anxiety.
- Treatments include hypnotic drugs, cognitive-behavioral therapy, and exercise.
Narcolepsy:
- Involves intense sleepiness during the daytime.
- Cataplexy (sudden loss of muscle tone for a few minutes while awake).
- Sleep paralysis (after waking or just before sleep for a few minutes).
- Hypnagogic hallucination (dream-like experiences while awake).
- Cause: Loss of orexin produced in the hypothalamus, which impacts sleep and appetite.
Sleep apnea: Loss of oxygen while sleeping due to a blockade of airway passages.
- Treated with continuous positive air pressure (CPAP) to keep airways open during sleep.
REM sleep behavior disorder (RBD):
- The sleeper does not undergo muscle paralysis during REM sleep and acts out dreams.
- More common in older males.
- No effective treatment; muscle relaxants provide some benefits.

Benefits of Sleep

Sleep and immune system function: Sleep deprivation weakens the immune system.
Removal of brain toxins: During sleep, the brain clears out waste products, including accumulated toxic proteins.
Memory consolidation: Some memories are consolidated during REM sleep, while others are consolidated during non-REM sleep.
Restorative effects: Sleep has restorative effects on mood and cognition and helps with weight maintenance.

Recap

Sleep is controlled by an endogenous biological clock and external cues (zeitgebers).
The suprachiasmatic nucleus (SCN) in the hypothalamus is the brain’s master clock.
Sleep is also controlled by a homeostatic factor that drives the need to catch up on sleep.
Sleep occurs in 5 stages: wake, NonREM1, 2, 3, and REM (rapid eye movement).
Sleep patterns vary with age and by species.
The thalamus plays a significant role in the alert state, and there is a disconnect between the thalamus and cortex during sleep.
Dreams can occur during all sleep stages but are most lucid during REM sleep.
Neurons in the brainstem inhibit motor neurons during REM sleep.
Sleep disorders include insomnia, sleep apnea, narcolepsy, and REM behavior disorder.
Sleep is beneficial for immune system function, memory consolidation, mood & cognition, restoration, and weight maintenance.