Sleep and Wakefulness Lecture Notes

Universita Zurich - Biomedicine II - Sleep and Wakefulness

Lecture Overview

Instructor: Hans-Peter Landolt, Institute of Pharmacology & Toxicology

• Course Code: BME 246

• Contact: landolt@pharma.uzh.ch

Learning Objectives:

• Explain physiological processes of sleep-wake regulation and the brain circuits governing these states.

• Identify major neurochemical systems promoting wakefulness and sleep.

• Understand that sleep is an active, regulated process.

• Explore the challenges in human sleep genetics relating to sleep-wake pathophysiology.

Slide 2: Learning Objectives

Key Points:

• Understand the physiological processes behind how we stay awake and fall asleep.

• Learn about the brain circuits that control the sleep-wake cycle.

• Identify the neurochemical systems that promote wakefulness and sleep.

• Recognize that sleep is an active and tightly regulated process, not just "switching off."

• Appreciate the genetic complexity of human sleep and the challenges in studying sleep disorders.

Explanation of Visuals:

• The slide has bullet points outlining the main goals of the lecture.

• No diagrams or data figures are present; this is a text-based overview.

Glossary:

• Sleep-wake regulation: Biological processes that control when we sleep and when we are awake.

• Neurochemical systems: Brain chemicals (like neurotransmitters) that influence sleep or alertness.

• Sleep pathophysiology: The study of dysfunctional sleep and its underlying biological causes.

Key Takeaway: This lecture will teach how the brain controls sleep and wakefulness, and why understanding these mechanisms is important for both science and health.

Slide 3: What don’t we know?

Key Points:

• Even after decades of research, fundamental questions about sleep remain unanswered.

• A major scientific review (Science magazine’s 125th anniversary) listed:

  • Why do we sleep?

  • Why do we dream?

• These are among the top unsolved questions in biology.

• The mystery of sleep continues to challenge scientists and drive research forward.

Explanation of Visuals:

• Cover of Science magazine showing “125 Questions” scientists still cannot answer.

• Highlights that sleep and dreaming are among the most puzzling biological phenomena.

Glossary:

• Dreaming: Mental experiences that occur during certain sleep stages, especially REM sleep.

• Scientific review: A published collection of major questions or findings in a field.

• REM sleep (mentioned contextually): A sleep stage associated with vivid dreaming and brain activity.

Key Takeaway: Despite decades of study, science still can’t fully explain why we sleep or dream, making sleep one of the biggest open questions in biology.

Slide 4: “Sleep as a Problem of Localization”

Key Points:

• Early researchers like von Economo studied brain damage in patients with sleep issues.

  • the saw a lot of people after the Spanish flu

  • the patients were a lot of sleeping like most hours of the day, only nutrition was consumed between the sleeps.

  • He examined brains of the patients and saw some l

• Damage to the posterior hypothalamus caused excessive sleepiness (lethargy).

• Damage to the anterior hypothalamus caused insomnia or trouble sleeping.

• These findings helped identify specific brain regions involved in regulating sleep.

Explanation of Visuals:

• Historical photo of von Economo, a pioneering sleep researcher.

• Diagram of the brain showing affected areas in:

  • Posterior hypothalamus (linked to narcolepsy, arousal)

  • Anterior hypothalamus (linked to sleep-promoting mechanisms)

• Labels show how different brain regions contribute to wakefulness and sleep.

Glossary:

• Hypothalamus: A brain region that controls many functions, including sleep, hunger, and temperature.

• Narcolepsy (=Schlaflähmung): A sleep disorder causing excessive daytime sleepiness and sudden sleep attacks.

• Encephalitis lethargica: A historical disease that helped identify brain areas related to sleep.

Key Takeaway: Brain studies showed that specific parts of the hypothalamus control sleep and wakefulness, revealing sleep as a function localized in the brain.

Slide 5: Brainstem Reticular Formation and Cortical Arousal

Key Points:

• The reticular formation in the brainstem plays a key role in waking the brain up.

• When this area is electrically stimulated, sleeping animals wake up.

• This helped discover the ascending reticular activating system (ARAS).

• The ARAS sends signals from the brainstem to the cerebral cortex to promote alertness.

Explanation of Visuals:

• Diagram of the brain shows the reticular formation in the brainstem and pathways reaching the cortex.

• Arrows indicate how electrical activation travels to different brain areas.

• A historical photo of Moruzzi & Magoun, who made key discoveries on ARAS.

Glossary:

• Reticular formation: A network of neurons in the brainstem that regulates arousal and sleep-wake transitions.

• Cerebral cortex: The outer layer of the brain involved in awareness, thought, and perception.

• Arousal: The state of being awake or alert.

• Electrical stimulation: Technique where brain areas are activated using small electrical currents.

Key Takeaway: The brainstem's reticular formation is essential for wakefulness, and stimulating it can awaken the brain—showing that arousal is actively controlled by deep brain structures.

Slide 6: Key Nuclei of the Ascending Arousal System

Key Points:

• Wakefulness is promoted by several brain nuclei that release arousal-promoting neurotransmitters.

• The hypocretin (orexin) system plays a critical role in stabilizing wakefulness.

• Key neurotransmitters include:

  • Noradrenaline (from locus coeruleus),

  • Serotonin (from raphe nuclei),

  • Histamine (from tuberomammillary nucleus),

  • Acetylcholine (from basal forebrain and brainstem),

  • Dopamine (from ventral tegmental area),

  • Orexin/Hypocretin (from lateral hypothalamus).

• These brain regions send activating signals to the cerebral cortex, keeping us awake and alert.

Explanation of Visuals:

• A labeled diagram shows arousal pathways ascending from the brainstem and hypothalamus to the cortex.

• Each neurotransmitter system is color-coded with arrows pointing to the cortex, indicating their wake-promoting action.

Glossary:

• Neurotransmitter: A chemical that nerve cells use to send signals.

• Locus coeruleus: Brain area that releases noradrenaline.

• Raphe nuclei: Produces serotonin, involved in mood and arousal.

• Basal forebrain: Region releasing acetylcholine to promote alertness.

• Orexin (Hypocretin): A neuropeptide important in stabilizing wakefulness.

• The tuberomammillary nucleus (TMN) in the hypothalamus is the sole source of histamine neurons in the brain, playing a critical role in regulating wakefulness, arousal, and various other physiological functions.

Key Takeaway: Wakefulness depends on a network of brain regions that use different neurotransmitters to stimulate the cortex and keep us alert.

Slide 7: Sleep as a Problem of Localization (Revisited)

Key Points:

• This is a recap of von Economo’s findings:

  • Posterior hypothalamus damage leads to excessive sleepiness.

  • Anterior hypothalamus damage causes insomnia.

• These findings were crucial in localizing sleep control in specific brain regions.

Explanation of Visuals:

• Same as Slide 4: A diagram showing the posterior hypothalamus (blue, associated with arousal) and anterior hypothalamus (orange, linked to sleep).

• Historical photo of von Economo included again, emphasizing his contribution.

Glossary:

• Localization: Identifying where a specific brain function occurs.

• Insomnia: Difficulty falling or staying asleep.

• Posterior hypothalamus: Region promoting arousal.

• Anterior hypothalamus: Region promoting sleep.

Key Takeaway: Sleep and wakefulness can be traced to specific brain areas, with different hypothalamic regions responsible for either promoting sleep or maintaining alertness.

Slide 8: Sleep-Active Neurons in VLPO & MnPO

Key Points:

• The VLPO (ventrolateral preoptic area) and MnPO (median preoptic area) are key sleep-promoting brain regions.

• Neurons in these areas become active during sleep and release GABA, an inhibitory neurotransmitter.

• These neurons suppress the arousal systems, allowing the brain to enter and maintain sleep.

Explanation of Visuals:

• Brain diagram highlights the VLPO and MnPO in the hypothalamus.

• Arrows show how these regions project inhibitory signals to arousal centers, blocking wake-promoting activity.

Glossary:

• VLPO (Ventrolateral preoptic nucleus): Brain area that helps initiate and maintain sleep.

• MnPO (Median preoptic nucleus): Another sleep-promoting region working with the VLPO.

• GABA (Gamma-aminobutyric acid): A neurotransmitter that inhibits neuronal activity, promoting calm and sleep.

• Thalamocortical loops are fundamental neural circuits, connecting the thalamus and cortex, crucial for sensory processing, motor control, and cognitive functions. These loops involve both direct and indirect pathways facilitating communication and integration of information between these brain regions.

• Thalamus: Serves as a relay station for sensory information and motor output, modulating signals before they reach the cortex.

• Cortex: Processes information received from the thalamus, leading to actions, thoughts, and emotions.

• Loops: Thalamocortical circuits involve both direct (thalamocortical pathways) and indirect pathways (through structures like the basal ganglia) that form closed loops, facilitating feedback and refinement of processing.

Key Takeaway: VLPO and MnPO neurons actively promote sleep by sending inhibitory signals to suppress arousal systems in the brain.

Slide 9: ‘Standard Model’: LHA/PH (Hcrt) Neurons Consolidate Waking

Key Points:

• The Lateral Hypothalamus (LHA) and Posterior Hypothalamus (PH) contain orexin (Hcrt) neurons.

• These neurons help maintain stable wakefulness by stimulating arousal systems.

• Loss of orexin leads to instability in sleep-wake transitions, such as in narcolepsy.

• The diagram shows a balance between sleep-promoting and wake-promoting forces.

Explanation of Visuals:

• A simplified balance scale illustration shows:

  • Sleep-promoting regions on one side (VLPO),

  • Wake-promoting regions (like orexin neurons) on the other.

• The image suggests that wakefulness is maintained when orexin neurons tip the balance.

Glossary:

• Orexin (Hypocretin): A neuropeptide that helps sustain wakefulness and prevent sudden sleep.

• Lateral hypothalamus (LHA): Brain area involved in arousal and motivation.

• Narcolepsy: A disorder caused by loss of orexin, leading to sudden sleep attacks.

Key Takeaway: Orexin neurons in the hypothalamus are crucial for keeping us awake and stabilizing the sleep-wake cycle.

Slide 10: ‘Standard model’: LHA/PH (Hcrt) Neurons Consolidate Waking & Sleep

Key Points:

• The LHA/PH (lateral/posterior hypothalamus) contains orexin (hypocretin)-producing neurons that regulate the sleep-wake switch.

• Orexin neurons stabilize wakefulness by activating arousal-promoting regions:

  • LC (Locus Coeruleus): releases noradrenaline

  • TMN (Tuberomammillary nucleus): releases histamine

  • Raphe nuclei: release serotonin

• These arousal systems suppress the VLPO, which promotes sleep.

• When orexin levels drop, the VLPO (Ventrolateral Preoptic Nucleus) becomes active and inhibits the arousal centers, leading to sleep.

• The model illustrates a flip-flop switch where either the wake- or sleep-promoting system is active, not both at once, enabling stable transitions.

• When orexin activity is high, the brain stays awake and alert.

• When orexin activity decreases, sleep-promoting neurons take over.

• The “standard model” illustrates a balance between wake and sleep centers.

Explanation of Visuals:

• A see-saw diagram shows:

  • Wakefulness: Orexin neurons activate arousal, VLPO is inhibited.

  • Sleep: VLPO suppresses arousal, orexin neurons are less active.

• Two face images represent the change between awake and asleep states.

Glossary:

• VLPO (Ventrolateral Preoptic Nucleus): Sleep-promoting brain region.

• Orexin (Hypocretin): Neurotransmitter that maintains wakefulness.

• LHA/PH: Lateral and posterior hypothalamus, regions where orexin neurons are located.

Key Takeaway: The balance between orexin neurons and VLPO determines whether the brain is awake or asleep, forming the core of the standard sleep-wake regulation model.

Slide 11: Sleep in Animals

Key Points:

• Sleep is a universal behavior seen across many species.

• Mammals and birds show similar postures and sleep states.

• Sleep is important for survival across evolutionarily diverse animals.

• The images illustrate the natural variation in sleep behavior, such as posture and environment.

Explanation of Visuals:

• Photos of sleeping animals, including dogs, lions, seals, and apes.

• Emphasizes that animals display similar rest behavior, often with closed eyes, reduced movement, and relaxed posture.

Glossary:

• Sleep states: Patterns or stages of sleep (like REM or deep sleep).

• Posture: The physical body position during sleep.

Key Takeaway: Sleep is a conserved and essential process found across species, indicating its fundamental biological importance.

Slide 12: Sleep-Wake Physiology: EEG, EMG, EOG

Key Points:

• The physiology of sleep is studied using three main recordings:

  • EEG (Electroencephalography): Measures brain wave activity.

  • EMG (Electromyography): Measures muscle activity.

    • Used also to measure the REM state sleeps

  • EOG (Electro-oculography): Measures eye movements.

    • Also used to measure in REM states

• These tools allow researchers to distinguish between sleep stages and monitor transitions between wakefulness and sleep.

• Each method targets a different physiological signal for a complete picture of sleep.

Explanation of Visuals:

• Top: A participant connected to sensors for EEG, EMG, and EOG.

• Bottom: Cartoon-style diagram showing:

  • EEG recording brain activity,

  • EMG from chin muscles,

  • EOG from eye movements.

• A mock EEG graph shows wave patterns on a screen.

Glossary:

• EEG (Electroencephalography): Records electrical activity from the brain via scalp electrodes.

• EMG (Electromyography): Tracks muscle tone using surface electrodes.

• EOG (Electro-oculography): Detects eye movements, especially during REM sleep.

Key Takeaway: EEG, EMG, and EOG are essential tools for analyzing brain, muscle, and eye activity during sleep and help identify different sleep stages.

Slide 13: Pioneers of Electroencephalography (EEG)

Key Points:

• This slide likely introduces the history of EEG and the scientists who developed it.

• EEG technology enabled the first scientific measurement of brain activity during sleep.

• Early EEG research laid the foundation for modern sleep physiology studies.

Explanation of Visuals:

• Image of a brain with electrode placements, highlighting where EEG signals are recorded.

• The slide sets up discussion of historical contributors (e.g., Hans Berger, although not named here).

Glossary:

• Electroencephalography (EEG): A method for recording electrical signals from the brain.

• Electrode: A small sensor placed on the scalp to detect electrical activity.

Key Takeaway: EEG technology, developed by pioneering scientists, was the breakthrough that allowed researchers to study brain activity during sleep scientifically.

Slide 14: Blockade of Alpha Rhythm by Opening of the Eyes

Key Points:

• The alpha rhythm (a type of brain wave) is typically seen when a person is awake but relaxed with eyes closed.

• Opening the eyes leads to an immediate disappearance of this rhythm.

• This phenomenon was first described by Hans Berger, the inventor of EEG, in 1929.

  • he was able to record changes in the brainwaves measured in different states.

• The alpha rhythm is a sign of restful wakefulness and reflects changes in brain state.

Explanation of Visuals:

• Top: Illustration of a brain with alpha waves.

• Left side bottom (EEG in yellow): Eyes closed – clear alpha rhythm visible.

• Right side bottom (EEG in yellow): Eyes open – alpha rhythm disappears.

Glossary:

• Alpha rhythm: A type of brain wave seen at approximately 10Hz (8–12 Hz), common when relaxed with eyes closed.

• EEG (Electroencephalogram): A recording of brain waves via scalp electrodes.

• Hans Berger: The German psychiatrist who developed the first EEG and discovered alpha rhythms.

Key Takeaway: The alpha rhythm is a marker of restful wakefulness and vanishes when we open our eyes, demonstrating how brain activity changes with sensory input.

Slide 15: Electroencephalography (EEG) – Electrode Placement

Key Points:

• EEG works by detecting the voltage difference between two electrodes placed on the scalp.

• Is nowadays used for measurements in diagnosis for example in epilepsie

• Electrode placement follows the 10-20 system (how to number the skull, the areas):

  • Even numbers = right hemisphere.

  • Odd numbers = left hemisphere.

  • Z = zero line (midline).

• Up to 256 electrodes can be used for high-resolution recordings.→ is called a high-density EEG (hdEEG), when you have more than 60 electrodes.

• Two types of measurements:

  • Referential (comparison to a fixed point).

  • Bipolar (difference between two active sites).

• How is the measurement with electrones done?

  • 1 Electrone is on the bone behind the ear (assumption is that in bone you have no EEG signal), than you have an electron in an active eEG area in the brain → you measure like this the differences of Activtiy vs. No Activtiy.

  • You have 2 electrons in two different active areas of the brain, so you measure the differences of these two active regions.

Explanation of Visuals:

• Diagrams show:

  • A head with EEG electrodes.

  • A schematic of brain regions and their corresponding electrode positions.

  • The 10-20 system grid for consistent electrode mapping.

Glossary:

• 10-20 system: A standardized method for placing EEG electrodes.

• Referential EEG: Measures brain activity relative to a reference point.

• Bipolar EEG: Measures voltage differences between two electrodes.

• Electrode: A small sensor used to record electrical signals from the scalp.

Key Takeaway: EEG measures voltage differences across the scalp using standardized electrode placement systems to monitor brain activity.

Slide 16: Features and Importance of EEG

Key Points:

• EEG reflects the brain state (e.g., wakefulness, sleep) through patterns like the alpha rhythm.

• Brain waves are produced by the collective behavior of cortical neurons.

• The human cortex contains ~16 billion neurons, and the entire brain has ~86 billion.

  • The downside is that you can’t get a picture or measurement of a single cell via EEG.

  • EEG is always the picture of the entire area of cells, showing the activity of the group of cells always.

• EEG offers a non-invasive, high-temporal-resolution view of brain activity.

• Sleep-related EEG patterns reflect complex interactions across brain regions.

• What you don’t have in EEG is a good spatial distribution, as you measure the concentration of many cells, not a single cell measurement.

Explanation of Visuals:

• Background shows EEG waveforms.

• Key points are listed to highlight:

  • Importance of EEG as a large-scale measure of cortical function.

  • Its usefulness for observing network-level brain activity, especially during sleep.

Glossary:

• Cortical neurons: Nerve cells in the brain’s cortex responsible for processing information.

• High temporal resolution: Ability to detect rapid changes in activity (on a millisecond scale).

• Network phenomena: Activity involving interactions between multiple brain areas.

Key Takeaway: EEG captures real-time brain dynamics, offering insights into how large populations of neurons coordinate during different brain states like sleep.

Slide 17: Generation of the Brain Waves (EEG)

Key Points:

• EEG signals do not directly detect action potentials (the spikes individual neurons use to communicate).

• Instead, they represent the summed activity of many neurons, especially their post-synaptic potentials (inputs).

• These potentials reflect the layered structure of the cortex, where large populations of neurons align in a way that their activity can be measured from the scalp.

Explanation of Visuals:

• Diagram of the cortical column:

  • Shows how inputs to dendrites of pyramidal neurons create electrical fields.

  • These fields add up to produce the EEG signal recorded at the scalp.

Glossary:

• Action potential: A brief electrical pulse that travels along neurons to transmit information.

• Postsynaptic potential (PSP): Electrical change in a neuron caused by receiving signals from another neuron.

• EPSP/IPSP: Excitatory/Inhibitory postsynaptic potentials.

• Pyramidal neuron: A type of large neuron in the cortex involved in generating EEG signals.

Key Takeaway: EEG signals arise from the summed electrical activity of many neurons' inputs—not their individual spikes—and reflect how brain circuits are functioning at a large scale.

Slide 18: EEG = Sum of Cortical Field Potentials

Key Points:

• EEG reflects the summed activity of many neurons, mainly their postsynaptic potentials.

• The example shows rhythmic spindle activity (~10 Hz), typical of sleep states.

• These rhythmic signals are generated by thalamo-cortical circuits.

• Only a few action potentials (spikes) are visible—most EEG activity comes from synaptic input, not spiking output.

Explanation of Visuals:

• Two lines:

  • Top trace: EEG signal showing spindle waves.

  • Bottom trace: Intracellular recordings showing small fluctuations (PSPs) and occasional spikes.

• Demonstrates the correlation between EEG and neuron input activity, especially during anesthesia or sleep.

Glossary:

• Field potentials: Electrical signals from many neurons' combined activity.

• Spindle activity: Bursts of ~10 Hz brain waves seen in sleep.

• Thalamo-cortical: Relating to connections between the thalamus and the cortex.

• PSP (Postsynaptic Potential): Electrical response in a neuron receiving input.

Key Takeaway: EEG signals mostly reflect the summed synaptic inputs to neurons rather than their spiking, particularly in sleep-related rhythmic patterns.

Slide 19: EEG Hallmarks of Wakefulness and Sleep

Key Points:

• EEG can distinguish between wakefulness and deep sleep based on wave patterns:

  • Wakefulness: Fast, low-amplitude beta/gamma oscillations.

  • Deep sleep: Slow, high-amplitude delta oscillations.

• These patterns are important markers of brain state.

Explanation of Visuals:

• Two simple EEG traces:

  • Top: Wakefulness – fast, small waves.

  • Bottom: Deep sleep – slow, large waves (delta rhythm).

    • you have much lower freq of signals, you have only 1-3 oscillations, high latency

• Labels show oscillation frequencies (~6 Hz for deep sleep).

Glossary:

• Beta/Gamma oscillations: Fast brain waves linked to attention and active thinking.

• Delta waves: Slow brain waves associated with deep sleep.

• Oscillations: Repeating wave patterns in EEG signals.

Key Takeaway: EEG wave patterns change dramatically between wakefulness and sleep, helping researchers identify different brain states.

Slide 20: Thalamo-Cortical Neuron Firing in Wakefulness vs. Sleep (Part 1)

Key Points:

• During wakefulness, thalamo-cortical neurons fire single spikes.

• These spikes support sensory processing and attention.

• In slow wave sleep, firing becomes more rhythmic and grouped (seen in next slide).

Explanation of Visuals:

• Left panel shows wakefulness:

  • EEG trace: low amplitude.

  • Neuron firing: isolated spikes, scattered in time.

• Highlights the shift in firing mode when transitioning to sleep.

Glossary:

• Thalamo-cortical neurons: Neurons connecting the thalamus and cortex.

• Single spikes: Individual, sharp action potentials.

• Wakefulness firing pattern: Neural activity suited for rapid information processing.

Key Takeaway: In wakefulness, thalamo-cortical neurons fire single spikes, supporting fast brain communication and sensory awareness.

Slide 21: Thalamo-Cortical Neuron Firing in Wakefulness vs. Sleep (Part 2)

Key Points:

• In slow wave sleep, neurons shift to a burst-pause firing mode:

  • Bursts of spikes followed by silent pauses.

• This pattern matches slow-wave EEG activity.

• Suggests the brain reduces sensory input processing during deep sleep.

Explanation of Visuals:

• Left: Wakefulness (as in Slide 20).

• Right: Deep sleep:

  • EEG shows large, slow waves.

  • Neuron trace shows “burst-pause” pattern—several spikes followed by a silent phase.

• Illustrates a clear shift from alert to sleep mode.

Glossary:

• Burst firing: A group of action potentials fired rapidly in a short period.

• Pause: A silent period with no spiking, following a burst.

• Slow wave sleep: Deep sleep stage characterized by slow EEG waves and reduced sensory input.

Key Takeaway: During slow wave sleep, thalamo-cortical neurons switch from single spikes to burst-pause firing, aligning with reduced sensory responsiveness.

Slide 22: Cortical Slow Oscillation (< 1 Hz)

Key Points:

• In slow wave sleep, the cortex displays very slow oscillations (<1 Hz).

• These alternate between:

  • Down-state: Neurons are silent (hyperpolarized).

  • Up-state: Neurons are active (depolarized).

• This was first recorded in cats and is now known as a fundamental feature of sleep physiology.

• Slow oscillations organize other brain rhythms during deep sleep.

Explanation of Visuals:

• EEG traces:

  • Wakefulness: Low-amplitude, fast signals.

  • Slow wave sleep: Large, rhythmic up-and-down waves.

• Intracellular recordings show how neuron membrane potential flips between up- and down-states.

Glossary:

• Hyperpolarization: A more negative membrane potential—neuron is less likely to fire.

• Depolarization: A more positive membrane potential—neuron is more likely to fire.

• Up-state / Down-state: Phases of activity and silence in neuron populations during sleep.

Key Takeaway: Slow oscillations during deep sleep reflect rhythmic shifts in neuron activity and silence, organizing other brain rhythms and playing a key role in sleep function.

Slide 23: EEG Patterns in Slow Wave Sleep

Key Points:

• EEG, EOG, and EMG recordings are used together to identify sleep stages.

• In slow wave sleep, EEG shows high-amplitude, low-frequency waves.

• These waves correlate with:

  • Muscle relaxation (seen in EMG),

  • Stable eye movements (seen in EOG),

  • Widespread cortical activation changes.

• Activity maps show changes in brain region involvement during sleep.

Explanation of Visuals:

• Diagrams of electrode placements and EEG/EOG/EMG signal types.

• Graphs show sleep-related slow waves, and spike raster plots show synchronous firing patterns.

• Brain activity maps indicate specific regions engaged during sleep.

• show case on bottom right shows that sleep is an active state in the brain as even during sleep, more “activity” is there than just “pauses”.

Glossary:

• EOG (Electro-oculography): Measures eye movements.

• EMG (Electromyography): Measures muscle tone.

• Spike raster: A plot of neuron firing over time.

Key Takeaway: Slow wave sleep is marked by synchronized brain activity, visible as large EEG slow waves, reduced muscle tone, and coordinated cortical signals.

Slide 24: Sleep Slow Waves – Thalamocortical vs. Cortical Network

Key Points:

• Sleep slow waves are generated by both:

  • Thalamocortical networks: Thalamus and cortex interactions.

  • Cortical networks alone: Internal cortical dynamics.

• These waves involve transitions between depolarized (up) and hyperpolarized (down) phases.

• Network diagrams illustrate how large neuron groups create these rhythmic transitions.

Explanation of Visuals:

• Left panel: Thalamocortical loop with bidirectional signals.

• Right panel: Cortical network activity with labeled up/down states.

• Shows both network types can generate the slow waves seen in deep sleep.

Glossary:

• Thalamocortical network: Communication loop between the thalamus and cortex.

• Cortical network: Neurons within the cortex interacting to produce rhythms.

• Network oscillation: Coordinated rhythmic activity across brain areas.

Key Takeaway: Both thalamocortical and cortical circuits contribute to the generation of sleep slow waves through synchronized transitions in neuronal activity.

Slide 25: Cortical and Subcortical Brain Circuits – Standard and Refined Models

Key Points:

• Sleep-wake regulation involves both cortical and subcortical circuits.

• Two models are presented:

  • Classical (standard): Linear pathways from brainstem to cortex.

  • Refined: Multiple interacting loops involving thalamus, hypothalamus, and cortex.

• Emphasis on reciprocal communication—not just top-down control.

• Models include the role of reticular activating system, hypothalamic sleep centers, and cortical feedback loops.

🟢 Wake-Promoting Circuits (green circle)

• BF (Basal forebrain) – ACh (acetylcholine)

• LH HCRT/OX (Lateral hypothalamus) – Orexin

• TMN (Tuberomammillary nucleus) – Histamine

🔵 Sleep-Promoting Circuits (blue circle)

• VLPO (Ventrolateral preoptic nucleus) – GABA, Galanin

⚫ REM-Promoting Circuits (black circle)

• VTA (Ventral tegmental area) – DA (dopamine)

• DRN (Dorsal raphe nucleus) – 5-HT (serotonin)

Explanation of Visuals:

• Diagram shows a flow from brainstem regions (green) up to cortex (blue).

• Refined model includes bidirectional arrows and feedback circuits, suggesting complex control.

Glossary:

• Subcortical: Brain regions below the cortex (e.g., brainstem, thalamus).

• Reticular activating system: Brainstem area that promotes arousal.

• Feedback loop: System where output influences future input, creating regulation.

Key Takeaway: Sleep-wake control involves dynamic communication between brainstem, hypothalamus, thalamus, and cortex—moving from linear models to complex interacting circuits.

Slide 26: Take Home Messages (I)

Key Points:

1. Wakefulness and sleep states are highly complex and finely tuned by small changes in multiple neurochemical systems.

2. The brain never truly "sleeps" — different network activity patterns occur in both wakefulness and sleep.

3. State transitions are regulated by organized neuronal ensembles that ensure smooth transitions between wake and sleep states.

Explanation of Visuals:

• Bullet points outline the key takeaways regarding the complexity of sleep-wake regulation.

• The visual emphasizes how sleep and wakefulness are intricately regulated by coordinated brain networks, adapting to external and internal signals.

Glossary:

• Neurochemical systems: Chemical messengers like neurotransmitters that regulate brain activity.

• Neuronal ensembles: Groups of neurons working together to control brain states.

Key Takeaway: Wakefulness and sleep are dynamically regulated by intricate brain networks and neurochemical systems, ensuring smooth transitions between states.

Slide 27: Wakefulness and Sleep are Tightly Regulated: The Two-Process Model of Sleep Regulation

Key Points:

• Sleep is regulated by two main processes:

  1. Homeostatic process: Responds to sleep debt by increasing the drive for sleep after prolonged wakefulness.

  2. Circadian process: Regulates timing of sleep based on the body's internal clock (e.g., peaks of alertness and sleepiness throughout the day).

• The graph shows a typical 24-hour cycle of sleep-wake regulation, with homeostasis increasing the drive for sleep after prolonged wakefulness.

Explanation of Visuals:

• The graph illustrates the interaction between:

  • Homeostatic process (blue), which increases the sleep drive with prolonged wakefulness.

    • If there is sleep taken away, the pressure of sleep depriviation (red curve) rises, and as soon sleep comes back, you fall to sleep faster → the curve is steeper downhill.

  • Circadian process (red), which peaks during typical sleep times (night).

• The intersection of these two lines shows the optimal timing for sleep, highlighting how both systems regulate sleep-wake cycles.

Glossary:

• Homeostasis: The body's process of maintaining internal stability, such as regulating sleep needs.

• Circadian rhythm: The body’s internal 24-hour clock that affects sleep, alertness, and temperature.

Key Takeaway: Sleep is regulated by a combination of homeostatic and circadian processes, which work together to maintain sleep-wake cycles.

Slide 28: Sleep Homeostasis

Key Points:

• Homeostatic mechanisms adjust the body's sleep needs based on sleep deprivation.

  • If sleep is cut short, the body increases the sleep propensity to recover.

  • The precise location of the homeostatic sleep mechanism in the brain is still unknown.

  • In contrast, the circadian mechanism (which governs sleep timing) is well localized in the suprachiasmatic nucleus (SCN) of the hypothalamus.

• Sleep propensity is influenced by the duration and intensity of previous sleep.

  • if you stay one night awake, and you sleep normally 8 hours, it doesn’t mean that you have to sleep the next day 16 hours in order to make up for the “lost” 8 hours of sleep. The intensity of the sleep is more intense and the body makes up for the lost hours.

• This process works alongside circadian rhythms, ensuring that we sleep enough to maintain optimal functioning.

Explanation of Visuals:

• The graph shows how sleep propensity increases after sleep deprivation and peaks when we reach the optimal sleep duration.

• The chart highlights how homeostasis interacts with circadian rhythms to regulate sleep needs.

Glossary:

• Sleep propensity: The body's increasing need for sleep after periods of wakefulness. Can be measured in the brain waes.

• Circadian process: The body's natural sleep-wake cycle, synchronized with the day-night cycle.

Key Takeaway: Homeostatic mechanisms adjust sleep needs based on deprivation, interacting with circadian rhythms to ensure optimal sleep duration and function.

Slide 29: Quantification of the EEG Signal

Key Points:

• Raw EEG signals represent brain activity, which can be analyzed to determine sleep stages.

• The power spectrum of the EEG signal helps identify specific frequencies associated with different brain states:

  • Wakefulness: Characterized by alpha oscillations (8-12 Hz).

  • Deep sleep: Characterized by slow-wave oscillations (0.5-4 Hz, delta waves).

• Quantifying the EEG helps to identify transitions between sleep and wake states.

🔁 What are Alpha and Delta Oscillations?

📊 What the Slide Shows

• Left side: Raw EEG signals (wavy line plots)

  • Top (Alpha): Fast, small waves during wakefulness.

  • Bottom (Delta): Large, slow waves during deep sleep.

• Right side: Power spectrum (how much “energy” there is at each frequency)

  • Top: Peak in the 8–12 Hz range, showing alpha waves dominate.

  • Bottom: Peak in the <4 Hz range, showing delta waves dominate.

🧩 Summary:

• Alpha waves = relaxed awake state, moderate frequency.

• Delta waves = deep sleep, very slow and strong signals.

Glossary:

• Alpha oscillations: Brain wave activity seen in relaxed wakefulness, with a frequency of 8-12 Hz.

• Delta waves: Slow, high-amplitude brain waves associated with deep sleep, typically in the 0.5-4 Hz range.

• Power spectrum: A graph showing the distribution of power across different frequencies in the EEG signal.

Key Takeaway: EEG analysis allows precise quantification of brain activity, distinguishing between wakefulness and sleep by identifying characteristic brain waves.

Slide 30: EEG Delta Activity as a Physiological Biomarker of Sleep Intensity (Sleep Homeostasis)

Key Points:

• Delta activity (0.5–4 Hz) in the EEG is a marker of sleep intensity and homeostatic sleep need.

• After sleep deprivation, delta power increases, reflecting greater sleep pressure.

• Delta activity is well measurable from EEG and also can be mathematically described, so based on the measurement of such an EEG you can see how long the brain is awake already.

• The graph shows the interaction of homeostatic (sleep pressure) and circadian (biological clock) processes over 24 hours.

Explanation of Visuals:

• Line graph plotting delta activity across time (y-axis: delta power; x-axis: clock time).

• Red line = homeostatic pressure (decreasing during sleep).

• Blue line = circadian rhythm (unchanged by sleep).

• Bars highlight when delta activity is highest and how it drops during sleep.

💡 What Is the Main Point of the Slide?

This slide illustrates the Two-Process Model of Sleep Regulation — a core concept in sleep science:

🔁 These two systems work together to regulate when you sleep, how long, and how deep.

🧠 Why Is This Important? (The Sense Behind It)

• The brain doesn’t just flip a switch when you go to sleep.

• Instead, it measures sleep need (via homeostasis) and timing (via circadian rhythms).

• Delta waves (measured via EEG) give scientists a reliable, objective marker of sleep intensity — especially for understanding:

  • Sleep deprivation effects

  • Recovery sleep after being awake too long

  • Sleep disorders like insomnia or hypersomnia

  • Why the first part of the night is deeper than the second

Glossary:

• Delta activity: Slow EEG waves indicating deep, restorative sleep.

• Sleep intensity: A measure of how deep or restorative sleep is.

• Sleep homeostasis: The body’s regulation of sleep need based on prior wakefulness.

Key Takeaway: EEG delta waves are a reliable physiological marker of how much the body needs and recovers from sleep, peaking early in the night when sleep pressure is highest.

Slide 31: Time Course of Physiological Variables During Nocturnal Sleep Recording

Key Points:

• Throughout the night, various physiological signals (EEG, EOG, EMG, respiration, body temperature) change in predictable patterns across sleep cycles.

• Sleep architecture cycles through REM and Non-REM stages roughly every 90 minutes.

• REM periods become longer and more frequent as the night progresses.

• Body functions like heart rate, breathing, and temperature shift across sleep stages.

Explanation of Visuals:

• Multi-panel graph shows overnight changes in:

  • Sleep stages (hypnogram),

  • EEG and EOG signals,

  • Temperature and movement.

• Colored bands represent different sleep stages, aligned with fluctuations in physiological signals.

Glossary:

• Hypnogram: A graph showing the sequence of sleep stages during the night.

• Nocturnal: Occurring at night.

• Physiological variables: Body functions such as temperature, movement, and respiration.

Key Takeaway: Sleep involves coordinated changes in multiple physiological systems, which cycle predictably through the night in alignment with REM and Non-REM sleep stages.

Slide 32: EEG, EOG, EMG Signatures Across Sleep Stages

Key Points:

• Different sleep stages can be identified using:

  • EEG: brain wave activity,

  • EOG: eye movements,

  • EMG: muscle tone.

• Wakefulness: fast EEG, eye movements, high EMG.

• NonREM Sleep progresses through:

  • Stage 1 (N1): Light sleep, theta waves.

    • Waves get slower

    • Is a transition phase (example of being in a ski-camp and just somehow hear what somebody says when in bed)

  • Stage 2 (N2): Spindles and K-complexes appear.

  • Stage 3/4 (N3): Deep sleep, dominated by slow waves.

  • REM sleep:

    • Wave movements from N3 are absent again

    • But there is movements from EOG showing the movements of Eyes

    • And complete absence of muscle tone which is minimal in REM state → therefore you need this measures otherwise you couldn’t discriminate between N1 and REM states.

• REM Sleep:

  • EEG resembles wakefulness,

  • EOG shows rapid eye movements,

  • EMG is flat (muscle atonia).

Explanation of Visuals:

• Side-by-side EEG/EOG/EMG traces show transitions from wake to deep sleep and REM.

• Circled features include K-complexes and sleep spindles.

• REM sleep EEG looks “awake-like” but with no muscle activity.

Glossary:

• K-complex: A high-amplitude EEG wave seen in N2, possibly involved in memory consolidation.

• Sleep spindle: A short burst of brain activity, seen in N2 sleep.

• Muscle atonia: Lack of muscle tone, characteristic of REM sleep.

Key Takeaway: Different sleep stages have distinct EEG, eye movement, and muscle activity patterns, which help classify sleep phases and understand brain-body dynamics during rest.

Slide 33: REM Sleep (“Paradoxical Sleep”) Shows Both Wake-Like and Sleep-Like Features

Key Points:

• REM sleep is called “paradoxical sleep” because:

  • The EEG resembles wakefulness (fast, low amplitude),

  • But the body is in deep muscle relaxation (atonia).

• REM involves active brain regions such as:

  • The pons, thalamus, and amygdala.

• This stage is critical for:

  • Dreaming,

  • Memory processing, and

  • Emotional regulation.

• REM is regulated by brainstem circuits and alternates with Non-REM stages in a regular rhythm.

Explanation of Visuals:

• Top: Brain diagram highlights brainstem circuits (REM-on and REM-off areas).

• Bottom: Hypnogram shows REM sleep occurring cyclically, especially in later parts of the night.

Glossary:

• REM (Rapid Eye Movement) sleep: A sleep stage marked by vivid dreams and rapid eye movements.

• Paradoxical sleep: Another name for REM, due to its unusual mix of active brain and inactive body.

• REM-on neurons: Brain cells that initiate and maintain REM sleep.

Key Takeaway: REM sleep uniquely blends active brain patterns with deep physical relaxation, playing a vital role in dreams, memory, and emotional health.

Slide 34: Three Main Dimensions of Human Sleep

Key Points:

• Human sleep is defined by three main dimensions:

  1. Physiology: Includes brain activity (EEG), eye movements, and muscle tone.

  2. Phenomenology: Subjective experiences such as dreams or sleep quality.

  3. Behavior: Sleep timing, duration, and observable patterns.

• REM and NonREM sleep occupy different areas in this 3D conceptual model.

• This multidimensional view helps to understand the complexity of sleep beyond just “being asleep.”

Wake on / REM on:

• Acetylcholine is high during awake phase

• gets low in Non-Rapid-Eyemoement phase (NREM)

• But than gets high again in REM stage

Wake on / REM off:

• Noradrenaline and Serotonin are present in Wake-Phase

• Get less in NREM phase

• And also decline in REM phase → compared to REM-on Acetylcholine.

Glossary:

• Phenomenology: Study of subjective experiences (e.g., dreaming, sleep perception).

• REM sleep: Sleep stage with vivid dreams and rapid eye movements.

• NonREM sleep: Deep sleep stages with slower brain waves and reduced consciousness.

Key Takeaway: Sleep is best understood through its physiological, behavioral, and experiential dimensions—each sleep state (REM, NonREM, wake) has a unique profile.

Slide 35: Sleep is a Rich and Complex Phenotype

Key Points:

• Sleep is influenced by multiple biological traits:

  • Chronotype (morning/evening preference),

  • Sleep duration,

  • Sleep architecture (distribution of sleep stages),

  • EEG wave patterns,

  • Homeostatic sleep pressure.

• These traits vary across individuals and are shaped by genetics and environment.

• Sleep should be viewed as a multifaceted phenotype, not a single state.

Explanation of Visuals:

• Images show diverse sleep environments and chronotypes (e.g., night owls vs. early birds).

• Bullet points list components that contribute to individual sleep differences.

Glossary:

• Chronotype: A person's natural preference for sleeping and waking times (e.g., night owl, morning lark).

• Sleep architecture: The structure and sequence of sleep stages across the night.

• Phenotype: Observable traits resulting from genetic and environmental influences.

Key Takeaway: Sleep is a complex and individualized biological trait made up of multiple measurable components like duration, brain waves, and circadian timing.

Slide 36: Molecular Regulation of Circadian Rhythms

Key Points:

• Circadian rhythms are controlled by a molecular feedback loop involving clock genes.

• Two main arms regulate the cycle:

  • Positive arm: CLOCK and BMAL1 genes activate the process.

  • Negative arm: PER1/2 and CRY1/2 genes inhibit the activation, creating a ~24h oscillation.

• This loop drives rhythmic expression of other genes and coordinates daily physiology, including sleep.

Explanation of Visuals:

• Diagram of the molecular feedback loop:

  • CLOCK and BMAL1 trigger PER and CRY gene transcription.

  • PER/CRY proteins accumulate, inhibit CLOCK/BMAL1 activity, and eventually degrade, restarting the cycle.

• Shows how this cycle regulates the expression of clock-controlled genes.

Glossary:

• Circadian rhythm: A biological cycle that follows a ~24-hour period, influencing sleep and other functions.

• Clock genes: Genes that drive the body’s internal timing system.

• Feedback loop: A regulatory system where the output of a process affects its own activity.

Key Takeaway: Circadian rhythms are regulated by molecular feedback loops involving clock genes, which generate daily cycles in gene expression and behavior.

Slide 37: Variants in ‘Clock Genes’ Cause Phase Shifts in Sleep-Wake Rhythms

Key Points:

• Mutations or variants in clock genes can shift the timing of the sleep-wake cycle.

• Common resulting phenotypes include:

  • Advanced Sleep Phase: Fall asleep and wake up early.

  • Delayed Sleep Phase: Stay up and sleep in later than usual.

  • Non-24-hour Rhythm: Sleep-wake cycle is not aligned with the 24-hour day.

  • Irregular Sleep-Wake Rhythm: Sleep is fragmented or inconsistent.

• These shifts are often seen in genetic disorders or in circadian rhythm sleep disorders.

Explanation of Visuals:

• Infographic shows four sleep timing phenotypes, each with a clock icon and actigraphy plots showing when sleep occurs.

• Illustrates how internal rhythms can become misaligned with external time (light-dark cycle).

Glossary:

• Phase shift: A change in the timing of the internal circadian clock relative to the environment.

• Actigraphy: A method to track sleep-wake patterns using a wearable device.

• Circadian rhythm disorder: A disruption in the natural sleep-wake timing.

Key Takeaway: Genetic variants in clock genes can cause misalignment between the biological clock and external time, leading to various sleep phase disorders.

🔑 Key Concepts & Explanations

• Our body has an internal biological clock that controls sleep-wake cycles (also called circadian rhythms).

• This clock is regulated by clock genes.

• Mutations (changes) in these genes can shift our sleep pattern earlier or later than normal.

• These shifts are called phase advances (earlier) or phase delays (later).

⏰ Phenotypes (Sleep Behavior Types)

🧬 Glossary

• Clock genes: Genes that regulate the circadian rhythm, helping the body know when to sleep and wake.

• Circadian rhythm: The natural 24-hour cycle of biological processes, including the sleep-wake cycle.

• FASPS (Familial Advanced Sleep Phase Syndrome): A genetic condition causing people to go to sleep and wake up very early.

• DSPS (Delayed Sleep Phase Syndrome): A condition where sleep and wake times are shifted much later than usual.

• PER2, PER3: Genes involved in the timing of the circadian clock.

• CKIδ / CKIε: Enzymes (Casein Kinase I delta/epsilon) that modify clock proteins and influence timing.

• Mutation: A change in the DNA sequence of a gene, which can affect how it works.

🖼 Visual Interpretation

• The timeline icons (sun 🌞 and moon 🌙) show when individuals tend to be awake or asleep.

• Black bars represent activity levels over a 24-hour period:

  • Early peaks for FASPS/morning larks.

  • Normal range in the middle.

  • Late activity for night owls and DSPS individuals.

✅ Key Takeaway

Variants in clock genes (like PER and CKI) can cause people to naturally sleep and wake much earlier or later than normal, leading to different sleep-wake behaviors (early birds vs. night owls). These changes are rooted in genetic differences and affect the timing of our internal biological clock.

Slide 38: Genetic Modifications in ‘Clock Genes’ Cause Sleep Phenotypes in Mice

Key Points:

• Genetic mutations in clock genes (e.g., Clock, Per, Cry, Bmal1) result in altered sleep behaviors in mice.

• These mutations affect:

  • Sleep timing (e.g., advanced or delayed sleep onset),

  • REM and NonREM sleep amounts,

  • Sleep fragmentation, and

  • Circadian amplitude.

• This research supports a genetic basis for sleep regulation and phenotypes.

Explanation of Visuals:

• A table lists key clock genes, the chromosome they’re located on, and their associated sleep phenotype when mutated in mice.

• Example phenotypes include shorter sleep, REM sleep reduction, or circadian rhythm disruption.

Glossary:

• Clock genes: Genes that regulate the body’s internal timing system.

• Phenotype: Observable traits resulting from genetic expression.

• REM/NonREM: Sleep stages with different brain activity patterns.

Key Takeaway: Genetic mutations in core clock genes cause distinct changes in sleep behavior in mice, reinforcing the genetic control of sleep regulation.

Slide 39: Normal Distribution of Habitual Sleep Duration

Key Points:

• In a large population sample (n=2,009), sleep duration follows a normal distribution.

• Most people sleep between 7 to 8 hours, but there is natural variability.

• Differences between work days vs. rest days are also observed.

• Genetic effects are small, suggesting a strong influence from environmental and lifestyle factors.

  • Many genes that are involved but most of them have a low contribution to the phenotype

  • The environmental factors, like if it is weekend or not, etc. have a higher impact is assumed.

  • Most of the Genes that contribute have most probably a less strong impact than the enviromental factors → e.g. like if you have the day free tomorrow or not

Explanation of Visuals:

• Bar graph shows the distribution of reported sleep durations on work days (grey) and rest days (white).

• The curve shows a bell-shaped pattern, typical of traits influenced by both genes and environment.

Glossary:

• Habitual sleep duration: The average amount of sleep a person usually gets.

• Environmental factors: Non-genetic influences like work schedule, light exposure, stress, etc.

Key Takeaway: While people vary in how long they sleep, sleep duration shows a normal population distribution and is influenced more by environment than by genetics.

Slide 40: Sleep EEG is a Genetically Determined Fingerprint

Key Points:

• Each individual has a unique and stable EEG pattern during sleep, much like a biological fingerprint.

• These patterns remain consistent across nights within individuals but differ between individuals.

• This indicates a strong genetic influence on sleep EEG characteristics, such as frequency and power of specific waves.

Explanation of Visuals:

• Three graphs:

  • Left: 4 individuals' EEG spectra, each showing distinct frequency peaks.

  • Middle: Same individuals over 4 nights → consistency across nights.

  • Right: 4 nights from one person → stable individual pattern.

Glossary:

• EEG spectrum: The range of brain wave frequencies recorded during sleep.

• Power: The intensity or amplitude of specific EEG frequencies.

• Fingerprint (metaphor): A unique and stable identifier.

Key Takeaway: Each person has a unique EEG sleep profile that remains stable across nights, highlighting the genetic basis of sleep brain activity.

Slide 41: Heritability of Sleep Phenotypes

Key Points:

• Several sleep-related traits have high heritability, meaning they are strongly influenced by genetics.

• Highly heritable traits include:

  • Sleep EEG characteristics (delta power, sigma/REM density),

  • Sleep duration,

  • Subjective sleep quality,

  • Chronotype (diurnal preference).

• Insomnia and restless leg syndrome show moderate genetic influence.

• Environmental influence still plays a role, especially for insomnia.

• The exact EEG measures is 96% reliant on a persons Genes!

  • meaning that if from multiple persons you would collect the EEGs over multiple nights, with Machine Learning, you are very likely able to detect back to which participant the EEG measures belonged to.

Explanation of Visuals:

• Bar chart shows heritability estimates (h² values) for different sleep phenotypes.

• Color-coded:

  • Orange = stronger genetic (gene-based) contribution,

  • Blue = stronger environmental contribution.

Glossary:

• Heritability (h²): The proportion of variation in a trait due to genetic differences.

• Phenotype: Observable characteristic, such as sleep duration or quality.

• Restless Leg Syndrome: A condition causing an uncontrollable urge to move the legs during rest.

Key Takeaway: Many aspects of sleep—especially EEG features, duration, and chronotype—are significantly shaped by genetics, though environmental factors remain influential.

Slide 42: The Sleep Homeostatic Response to Sleep Deprivation in Humans is Heritable

Key Points:

• A scientific study published by the Sleep Research Society shows that how a person responds to sleep deprivation is influenced by genetics.

• The homeostatic sleep response—how the brain compensates for lost sleep—varies between individuals and is heritable.

• This means that individual vulnerability or resilience to sleep loss has a genetic basis.

• Identifying these genetic components may help explain why some people are more affected by sleep loss than others.

Explanation of Visuals:

• The slide shows a screenshot of the journal article's title and summary.

• The study supports the idea that sleep recovery mechanisms after deprivation are not purely environmental but partly encoded in our DNA.

Glossary:

• Sleep deprivation: Not getting enough sleep, either acutely or chronically.

• Homeostatic response: The body’s automatic compensation for lost sleep, often seen as increased sleep pressure or delta activity.

• Heritable: Able to be passed down genetically from parents to offspring.

Key Takeaway: The brain’s ability to recover from sleep deprivation is genetically influenced, highlighting that sleep homeostasis has a strong biological foundation.

Slide 43: Genetic Architecture of Sleep-Related Traits

Key Points:

• Genome-wide association studies (GWAS) have identified many genes linked to sleep-related traits.

• These genes are spread across multiple chromosomes, affecting traits like:

  • Sleep duration,

  • Sleep onset timing,

  • Circadian rhythm regulation,

  • EEG features during sleep.

• Understanding the genetic architecture of sleep can help identify molecular pathways that regulate sleep and wakefulness.

Explanation of Visuals:

• A genetic map showing associations between specific genetic loci and sleep phenotypes across different chromosomes.

• Colored markers indicate gene regions associated with different sleep traits, based on large-scale population studies.

Glossary:

• GWAS (Genome-Wide Association Study): A method to scan genomes for variants associated with traits or diseases.

• Genetic loci: Specific locations on chromosomes where genes or variants are found.

• Genetic architecture: The underlying genetic makeup contributing to a complex trait.

Key Takeaway: Numerous genetic regions contribute to individual differences in sleep, revealing sleep as a polygenic trait shaped by many interacting genes.

Slide 44: Take Home Messages (II)

Key Points:

1. Sleep is not passive—it is an active, regulated biological process.

2. Major sleep characteristics—including EEG patterns and state transitions—are under genetic control.

3. Understanding the genetic basis of sleep will help identify the molecular mechanisms involved and give insight into why we sleep.

Explanation of Visuals:

• A clean bullet-point summary that reinforces the key insights from the lecture:

  • Sleep is biologically regulated,

  • Its features are heritable,

  • Research into sleep genes helps uncover the purpose and function of sleep.

Glossary:

• EEG (Electroencephalography): A technique that records electrical brain activity, often used to study sleep.

• Molecular mechanisms: The biological processes at the cellular level that control functions like sleep.

Key Takeaway: Sleep is actively controlled by our genes and brain circuits, and understanding its genetic regulation will bring us closer to discovering the true function of sleep.

🔍 Here’s what the slide is saying in simple terms:

1. Sleep is not just passive rest — it's an active, highly regulated process in the brain and body.

2. Many of its features (like EEG patterns and when we sleep/wake) are influenced by our genes.

3. But — and this is the key point — although we know how sleep is regulated, we still don’t fully understand why we sleep — meaning, the exact functions of sleep are still not completely clear.

🧠 So, do we know the function of sleep?

• We have several strong theories, such as:

  • 🧹 Brain cleanup (e.g., clearing waste via the glymphatic system)

  • 🧠 Memory consolidation (especially in REM and deep sleep)

  • 🧬 Cell repair & immune system support

  • 🔌 Energy conservation & reset

But there's no single, complete explanation yet — and that’s why researchers are still trying to identify the key genes and molecular mechanisms to better understand sleep’s full biological purpose.

Let me know if you’d like a short glossary-style summary of the leading theories of sleep function!