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Cirkadiansk rytm, sömn och medvetande.pdf
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Cirkadiansk rytm, Sömn och Medvetande Eric Hanse HT 2025
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Circadian rhythms appeared 2-3 billions years ago Sleep, like ageing17,18, may be an inescapable consequence of aerobic metabolism.
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Circadian organization in mammals Hastings et al 2018 Nat Rev Neurosci 19:453-469
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The central clock in nucl. suprachiasmaticus (SCN) synchronizes circadian rhythms Control After lesion of the SCN
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Model for the circadian clock
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The molecular clock is based on delayed negative feedback
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The SCN does not keep an exact 24 hour cycle if not entrained ”The third eye” -melanopsin-containing ganglion cells sleep wake
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SCN signals to the rest of the brain and body both electrically and with hormones Higher frequency of action potentials during the day Homones, for example: Cortisol – highest levels when we wake up Melatonin – a “dark hormone”, released from corpus pineale Welsh et al (1995) Neuron 14:697
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Pracucci et al 2023 Nat Comm 14:7108 Alfonso et al 2023 Nat Neurosci 26:64-78 I.c.[Cl-] is higher during wake and lower during sleep in cortical pyramidal neurons
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Sleep “Sleep is the readily reversible state of reduced responsiveness to and interaction with the environment”
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Why do we sleep? Processing of memories ”Brain wash” Hauglund et al 2025 Cell 188: 1-17 Brodt et al 2023 Neuron 111: 1050-1075
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NA, 5-HT, Histamin High Low Very Low Ach High Low High Orexin High Low Low Energy consumption High Somewhat lower High Awake, NREM and REM Hobson (2005) Nature 437:1254
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The ”wake nucleus” in the hypothalamus (LHA) excites the modulatory transmitter systems using Glu/Orexin Saper et al (2005) Nature 437:1257 LC –Locus Coeruleus BF – Basal forebrain LH – Lateral Hypothalamus VLPO – VenteroLateralPreOptic TMN - TuberoMammillary Nucl LDT/PPT – LateroDorsal- and PeduncoPontine Tegmental nucl
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The ”sleep nucleus” in the hypothalamus (VLPO) inhibits the modulatory transmitter systems using GABA/Galanin Saper et al (2005) Nature 437:1257
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The cells in LHA and VLPO are under circadian control by the SCN via the DMH in the hypothalamus Saper et al (2005) Nature 437:1257
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SCN DMH VLPO GABA/Galanin NA, 5-HT, NA, ACh Light Meals, Temperature, Emotions / Cognition
LHA Orexin +
Somnogenic factors Somnogenic factors +
Sleep control
Somnogenic factors
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Adenosine is an ”somnogenic” factor contributing to sleep pressure
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Three different brain states: Wake, NREM & REM Wake Non-REM REM NA, 5-HT, Histamin High Low Low ACh High Low HIGH Orexin High Low Low EEG Desynchronized Synchronized Desynchronized Energy consumption High Moderate High Muscle tonus High Moderate Low Breating / Heart rate Regular Regular Oregelbunden Temperature regulation Functioning Functioning Non-functioning Eye movements Vision Slow Fast (REM)
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Timofeev & Chauvette (2018) Neuron 97:1200-1202 Modulatory transmitters and changes of e.c. ion conc. regulate the activity of cortical neurons EMG I.c. EEG
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An optimal level of neuronal network activity in the brain - Criticality Hengen & Shew (2025) Neuron 113:1-17
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Loss of consciousness during sleep and anaesthesia because ”decoupling” of cortical pyramidal neurons? Marvan et al (2021) Neurosci Conscious 7: 1-17
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Cortical pyramidal neuron with two action potential initiation zones comparing Content with Context Granato et al 2024 Neurosci and Biobehav Rev 161: 105688 ”Predictive coding” and ”Predictive error”
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Simultaneous apical feedback and basal feedforward inputs provide synergistic firing output Larkum (2012) TiNS 36:141-149
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Promoting apical and basal coupling enables consciousness Suzuki & Larkum (2020) Neuron 180: 666-676
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