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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.