Sleep_neurobiology___circadian_biology

Sleep Mechanisms: Neurobiology & Circadian Biology

• Overview of important factors influencing sleep

Introduction

• Centre for Sleep Science at UWA focuses on research and education regarding sleep disorders and mechanisms.

Key Personnel

• Jen Walsh, PhD

  • Director of the Centre for Sleep Science, UWA

  • Senior Research Fellow, West Australian Sleep Disorders Research Institute, SCGH

  • Lecturer

Learning Outcomes

• Understand fundamental neuron function, structure, and communication

• Summarise understanding of adenosine as a sleep-promoting neurochemical agent

• Identify anatomical regions that regulate circadian rhythms

• Explain role of neurotransmitters in inhibitory & excitatory synapse activity

• Recall major neurotransmitters involved in sleep and wakefulness

Outline of Topics

1. Circadian Biology

2. Neural Communication – Chemical Synapses

3. Neuron Structure & Function

4. Other Sleep-Promoting Neurochemical Agents

5. Neurotransmitters Involved in Sleep

6. Inhibitory & Excitatory Synapses

Neuron Structure, Function & Communication

• Neurons: relay neural impulses to and from organs, muscles, and other neurons

• Components of Neurons:

  • Cell Body

  • Dendrites

  • Axon

  • Synaptic End Bulb/Axon Terminal

• Neuron Function

  • Pre-synaptic and Post-synaptic neuron roles

Chemical Synapses & Neurotransmitters

• Pre-synaptic neuron: releases neurotransmitters into the synaptic cleft

• Post-synaptic neuron: contains neurotransmitter receptors

• Process involves neurotransmitter reuptake pumps and synaptic vesicles

• Neurons can be classified as excitatory or inhibitory based on neurotransmitter effects.

GABA (Inhibitory Synapse)

• GABA (Gamma-aminobutyric acid)

  • Binds to GABA receptors, leading to inhibition of the post-synaptic neuron

  • Drugs can modify GABA's effects

Effects of Benzodiazepines & Alcohol

• Without these substances, the synapse functions normally

• With benzodiazepines & alcohol: increases GABA effect leading to more inhibition

Dopamine (Excitatory Synapse)

• Role in synapse function:

  • Pre-synaptic neuron releases dopamine

  • Dopamine receptors facilitate excitatory signals in the post-synaptic cell

Dopamine Synapse Agonists & Antagonists

• Agonists: Enhance dopamine effects (e.g., amphetamines)

• Antagonists: Block receptor activation (e.g., promethazine)

Neurotransmitter Activity Levels in Sleep-Wake States

• Wake State: High norepinephrine, dopamine, and acetylcholine

• NREM: Varying levels of neurotransmitters such as GABA and serotonin

• REM: Dominated by acetylcholine activity

Brain Structures in Sleep-Wake Regulation

• Main structures involved:

  • Norepinephrine: Locus coeruleus

  • GABA: Ventrolateral preoptic nucleus

  • Glutamate: Cortex

  • Orexin/Hypocretin: Lateral hypothalamus

  • Dopamine: Ventral tegmental area

  • Serotonin: Raphe nucleus

  • Histamine: Tuberomammillary nucleus

Sleep-Promoting Neurochemical Agents (Somnogens)

• Key agents include:

  • Proinflammatory cytokines (e.g., IL-1β and TNFα)

  • Prostaglandin D2

  • Growth hormone releasing hormone

  • Adenosine: Influential in promoting sleep through neurochemical pathways

Adenosine Function

• By-product of ATP depletion, leading to increased levels throughout the day.

• Effects on Sleep: Infusion promotes sleep; caffeine acts as an antagonist, promoting wakefulness.

Circadian Biology

• Central clock located in the suprachiasmatic nucleus

• Peripheral clocks present in various organs (e.g., liver, pancreas)

• Key influences on circadian rhythm:

  • Light

  • Feeding

  • Exercise

  • Social activities

  • Hormones

Brain Structures Involved in Sleep Timing

• Structures similar to sleep regulation also play roles in circadian timing (e.g., reticular formation, pineal gland for melatonin regulation).

Summary Points

1. Neurons and neurotransmitters in the brainstem regulate sleep & wake stages.

2. Excitatory and inhibitory neurotransmitter functions are critical.

3. Sleep-promoting neurochemical agents like adenosine have significant roles.

4. Many drugs can modify neurotransmitter activity.

5. Both central and peripheral structures are key for circadian regulation.

Further Reading

• McGinty & Szymusiak, Chapter 7: Neural Control of Sleep in Mammals, Principles and Practice of Sleep Medicine, 7th ed., 2021.

• Fuller, Zee, Buxton, and Avidan, Chapter 3: Sleep Mechanisms, Atlas of Clinical Sleep Medicine, 3rd ed., 2024.

• Esapna & Scammell, Sleep neurobiology from a clinical perspective, SLEEP 2011; 34:845-858.