L6 : sleep neurobiology and circadian biology

What are the three main parts of a neuron

• Cell body (soma) – Contains the nucleus, controls the cell’s function.

• Dendrites – Receive incoming signals from other neurons.

• Axon – Sends electrical impulses to other neurons, muscles, or gland

What is a synapse, and what happens there?

• A synapse is the junction between two neurons where signals are transmitted.

• Neurotransmitters are released from the presynaptic neuron, cross the synaptic cleft, and bind to receptors on the postsynaptic neuron

What is the difference between chemical and electrical synapses?

• Chemical synapses use neurotransmitters to transmit signals.

• Electrical synapses use direct ion flow through gap junctions for faster communication

What is GABA, and how does it promote sleep?

• Gamma-Aminobutyric Acid (GABA) is the brain’s primary inhibitory neurotransmitter.

• Reduces neural activity, promoting sleep and relaxation.

How do benzodiazepines and alcohol affect GABA synapses?

• Both act as GABA agonists, enhancing inhibition.

• Increase drowsiness but can reduce sleep quality

What is dopamine, and how does it regulate wakefulness?

• Dopamine is an excitatory neurotransmitter that increases alertness and motivation.

• High dopamine levels promote wakefulness

What happens when dopamine agonists are taken?

• Increase dopamine levels by stimulating dopamine receptors.

• Example: Amphetamines, which boost wakefulness

What do dopamine antagonists do?

• Block dopamine receptors, reducing excitatory activity.

• Example: Promethazine, used for sedation

What neurotransmitters are active during wakefulness?

• Acetylcholine (Basal forebrain, Pons)

• Norepinephrine (Locus coeruleus)

• Dopamine (Ventral tegmental area)

• Histamine (Tuberomammillary nucleus)

• Orexin (Hypocretin) (Lateral hypothalamus)

Which neurotransmitters promote sleep?

• GABA (Ventrolateral preoptic nucleus, Brainstem)

• Melanin-Concentrating Hormone (MCH) (Locus coeruleus)

• Serotonin (Raphe nucleus

What brain structures regulate wakefulness?

• Locus coeruleus (Norepinephrine)

• Tuberomammillary nucleus (Histamine)

• Lateral hypothalamus (Orexin)

• Basal forebrain & Pons (Acetylcholine)

What brain regions are involved in sleep?

• VLPO (Ventrolateral Preoptic Nucleus) – Inhibits wake-promoting neurons.

• Locus Coeruleus – Reduces norepinephrine activity.

• Raphe Nucleus – Releases serotonin to modulate sleep stages.

What is the reticular formation, and what does it do?

• A network in the brainstem that regulates wakefulness and sleep transitions

Q: What is orexin/hypocretin, and what condition is associated with its deficiency?

• Stabilizes wakefulness.

• Narcolepsy is caused by orexin deficiency

What is adenosine, and how does it influence sleep

• Builds up during wakefulness and promotes sleep pressure.

• Blocked by caffeine, leading to alertness

Q: How does caffeine affect sleep?

• Blocks adenosine receptors, reducing sleep pressure.

• Can delay sleep onset and reduce deep sleep

What are somnogens, and what are some examples?

• Substances that promote sleep.

• Examples:

  • Adenosine

  • Pro-inflammatory cytokines (IL-1β, TNFα)

  • Prostaglandin D2

  • Growth Hormone-Releasing Hormone (GHRH)

Where is the body’s master circadian clock

• The Suprachiasmatic Nucleus (SCN) in the hypothalamus

How does the SCN regulate sleep

• Detects light via the retina and suppresses melatonin release.

• Darkness triggers melatonin secretion from the pineal gland

What are peripheral clocks, and where are they found?

• Found in liver, muscles, fat tissue, and gut.

• Regulated by feeding, exercise, and social cues

• Adrenal Muscle Liver Pancreas Gastrointestinal Reproductive Adipose tissue Lymphatic

What genes control the circadian clock?

• CLOCK & BMAL1 – Activate circadian rhythm genes.

• PER & CRY – Suppress clock activity

What are zeitgebers, and what is the strongest one?

• Environmental cues that reset the circadian clock.

• Light is the strongest zeitgeber.

What factors influence circadian rhythm

• light exposure

• Feeding schedule

• Physical activity

• Social interactions

What is the role of the pineal gland?

• Produces melatonin.

• Regulated by the SCN

What happens when the circadian clock is misaligned?

Leads to sleep disorders, metabolic issues, and cognitive impairments

What is shift work disorder

• Misalignment between work schedule and circadian rhythm, leading to poor sleep