Sleep and Circadian Rhythm

How can we study someone’s sleep?

Polysomnography: brain waves (EEG), eye movements (EOG), muscle movements (EMG)

How is Sleep Characterized

Decrease in physical activity, the body uses about 10% less energy. A decoupling from external inputs, heightened threshold for detection of sensory stimuli. Changes in brain wave activity, EEG (electroencephalography).

Phases of Sleep

Based on EEG readings, we can try and determine what phase of sleep someone is in. Originally 2 phases: REM or rapid eye movement and non-REM sleep. Now we have 4 phases: NREM1, NREM2, NREM3, REM.

NREM 1

Relaxed wakefulness, drowsiness. Transition period between wakefulness and sleep. Lasts around 5 to 10 minutes.

NREM 2

About 50% of a night’s sleep is in NREM2. Body temperature drops and heart rate begins to slow. Brain begins to produce sleep spindles lasts approximately 20 minutes.

NREM 3

Deep sleep, lowest physiological activity of the night. Muscles relax. Muscles pressure and breathing rate drop. Deepest sleep occurs.

REM

Paradoxical sleep; muscles immobile, except for the eyes. When we dream. Brain becomes more active. Body becomes relaxed and immobilized. Dreams occur. Eyes move rapidly.

Paradoxical

Person is asleep, muscles are not moving but eyes are moving rapidly

Awake Phase of Sleep

Dominated by high-frequency waves - beta band range of frequencies: 13-30Hz.

NREM1 Phase of Sleep

Beta frequency amplitude decreases to alpha waves (8-13 Hz) and then theta waves (4-8 Hz)

NREM 2 Phase of Sleep

Theta waves predominate with two interruptions that may be related to learning and memory. K - Complexes and sleep spindles.

K- Complexes

Large amplitude events that are observed about every minute.

Sleep Spindles

A high frequency burst of rapid neural activity in the low beta range that lasts for a second.

NREM 3 Phase of Sleep

Cortical neurons fire in synchronicity with one another; changes in potentials cause large amplitude deflections in the EEG, in the delta band (1-4 Hz)

REM Phase of Sleep

Pattern of activity very similar to being awake.

How can we graph/illustrate a person’s sleep experience?

Using a hypnogram

Stages of Sleep Deprivation Stage 1

Sleep deprivation for 24 hours. Cognitive impairment begins, memory fades, emotional instability & increased stress hormones.

Stages of Sleep Deprivation Stage 2

36 hours of sleep deprivation. Microsleeps occur, cognitive abilities decline, and anxiety and irritability increase.

Stages of Sleep Deprivation Stage 3

Sleep loss for 48 hours. Hallucinations, delusions, muscle weakness & inflammation intensify, affecting physical & mental health.

Stages of Sleep Deprivation Stage 4

72 hours of sleep deprivation. Thoughts disorganize, speech becomes incoherent, psychosis sets in, and physical deterioration worsens.

Stages of Sleep Deprivation Stage 5

More than 72 hours of lack of sleep. Constant hallucinations, seizures, organ failure, and death are likely without medical intervention.

Why do we Sleep?

The lack of sleep results in mental and physical fatigue, poor decision-making, impaired learning, emotional irritability, and an increased risk of migraine and epileptic seizures. Chronic insomnia results in death. We have little understanding of how sleep ‘restores’ the brain.

In a paper published in 2013 it was shown that:

The extracellular space in the brain of an awake mouse accounts for 14% of the brain volume and during sleep this increases to 23%. CSF flows through extracellular space and this flow increases to 95% during sleep. Norepinephrine is responsible for loss of the extracellular space when awake. Beta amyloid (peptide in Alzheimer’s disease) is cleared from extracellular space during sleep.

Theories on why we sleep

Recuperation theory, evolutionary adaptation theory, brain plasticity theory

Recuperation Theory

The body needs a period of time when energy usage decreases and the body’s natural repair systems can work without interruption. Enhanced metabolic cleaning during sleep. Immune system function improved with sleep. Increased production of growth hormone during sleep.

Evolutionary Adaptation Theory

Sleep patterns are different across species for reasons that most efficiently benefit the animal. Humans - dangerous in the dark, so sleep. Dolphins - the ability to put one half of their brain to sleep at a time so awake side can detect predators.

Brain Plasticity Theory

Brain needs some period of time for critical changes to occur. Academic performance and exam grades worsen the less sleep one gets. Memory consolidation. Declarative memory and procedural memory

Declarative Memory

Information about facts benefits from slow-wave sleep.

Procedural Memory

The learning of motor skills - enhanced by REM sleep

What are circadian rhythms? Chronobiology

The study of biological clocks and biological rhythms within an organism. Cycles of gene transcription. Hormone surges. Patterns of fatigue and alertness.

Rhythm

A repeating event that occurs with a regular pattern.

Period

Duration of time it takes one cycle of the rhythm to occur.

Phase

Describes a marker or point in a daily rhythm

What are circadian rhythms?

Biological rhythms are endogenous and entrainable. If humans or animals are kept in darkness or constant dim light they still show a ~24-hour cycle of activity, rest/sleep. The time between waking up each day in these conditions is the free-running period. Human free-running period is 23.5-24.7h/day. The rhythm is entrainable to external cues to stay synchronized with the environment. Rhythms entrain in response to zeitgebers- time givers Environmental cues such as when the sun comes up; increased sensory input from those around you.

Sleep Related Neurochemical Signals

Overall we know the following: Glutamate, GABA, Norepinephrine. There are three specific sleep-related neurotransmitters to take note of: Adenosine, Melatonin, and Histamine

Glutamate

Signaling heightened during awake state; increases during REM

GABA

Drugs that increase GABA are used as sedatives and sleep aids

Norepinephrine

Enhances alertness

Adenosine

Variety of functions; the “A” in DNA; involved in inflammation, immune response, and modulation of heart rate. Also part of ATP- adenosine triphosphate. Throughout the day as our energy consumption increases, so do adenosine levels, signaling to the brain that we are sleepy. The most common psychostimulant drug in the world antagonizes the adenosine receptor: caffeine

Melatonin

An endogenous hormone that helps the brain regulate the sleep-wake cycle. Pineal gland converts tryptophan to melatonin, which is then released into the bloodstream, signaling the body to prepare for sleep. Dependent on exposure to sunlight. Cells in the retina communicate whether it is daytime or not. These specific cells send axons along the retinohypothalamic tract, synapsing on an area of the hypothalamus known as the suprachiasmatic nucleus (SCN). Cells of the SCN project to the pineal gland. During the day - SCN inhibits pineal gland; low melatonin. As daylight decreases - the SCN sends out a weaker signal, hence an increase in melatonin from pineal gland.

Histamine

Mediates the sensation of itch, participates in the inflammatory response, and activates the immune system. In the brain, histamine acts as a pro-wakefulness neurotransmitter (the opposite of adenosine and melatonin). Antihistamines are currently Dr. Mitrano’s way to survive this pollen.

Where are rhythms in the brain?

The suprachiasmatic nucleus: The master clock. Connection to the pineal gland and melatonin.

Where are rhythms in the brain step 1

Blue wavelength light activates intrinsically photosensitive retinal ganglion cells (ipRGCs) in the retina which activate the SCN.

Where are rhythms in the brain step 2

SCN cells project to neurons in the spinal cord, which project back to the pineal gland inhibiting it. Pineal cells secrete melatonin in the bloodstream so SCN activation reduces melatonin secretion.

Where are rhythms in the brain step 3

Pineal cells reduce their secretion of melatonin in the blood stream.

The suprachiasmatic nucleus Melatonin as a medical treatment

Insomnia, jet lag, circadian rhythm and shift work sleep disorder, to help support sleep in the elderly

Brain structures involved in sleep: More on the Hypothalamus

Tuberomammillary nucleus: major site of neuronal production of the wakefulness neurotransmitter histamine. The lateral hypothalamus has neurons that produce wakefulness neurotransmitter orexin. These neurons are lost in someone with severe narcolepsy.

Brain structures involved in sleep: Reticular Formation

The reticular formation: found in the brainstem - present throughout the midbrain, pons and medulla. Typically, the reticular formation is regions of the brainstem between clearly defined nuclei and tracts. It is groups of neurons embedded in a seeming disorganized mesh of axons and dendrites. Upward pathway from reticular formation to cortex is also called the ARAS - ascending reticular activating system. Downward pathway - the reticulospinal tract is involved in motor control and not associated with sleep. The reticular activating system from midbrain and pons is required for wakefulness. Noradrenergic neurons in the locus coeruleus and serotonergic neurons in the raphe nucleus of the reticular formation project to cortex and are required for wakefulness.