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  • Perspective
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Overnight neuronal plasticity and adaptation to emotional distress

Nature Reviews Neuroscience volume 25, pages 253–271 (2024)Cite this article

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Abstract

Expressions such as ‘sleep on it’ refer to the resolution of distressing experiences across a night of sound sleep. Sleep is an active state during which the brain reorganizes the synaptic connections that form memories. This Perspective proposes a model of how sleep modifies emotional memory traces. Sleep-dependent reorganization occurs through neurophysiological events in neurochemical contexts that determine the fates of synapses to grow, to survive or to be pruned. We discuss how low levels of acetylcholine during non-rapid eye movement sleep and low levels of noradrenaline during rapid eye movement sleep provide a unique window of opportunity for plasticity in neuronal representations of emotional memories that resolves the associated distress. We integrate sleep-facilitated adaptation over three levels: experience and behaviour, neuronal circuits, and synaptic events. The model generates testable hypotheses for how failed sleep-dependent adaptation to emotional distress is key to mental disorders, notably disorders of anxiety, depression and post-traumatic stress with the common aetiology of insomnia.

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Fig. 1: The systems, circuit and molecular levels of a memory trace.
Fig. 2: Increased synaptic communication through noradrenergic signalling.
Fig. 3: Memory trace consolidation through late-phase LTP inducing activity in cortico-hippocampal circuits.
Fig. 4: Neuromodulatory milieu and neurophysiology across wakefulness and sleep.
Fig. 5: A proposed mechanism to remap a novel memory trace onto the familiarity-encoding pathway.
Fig. 6: Depotentiation of amygdala–hippocampal connections through in-phase and anti-phase theta frequency coupling during REM sleep.
Fig. 7: Proposed model of memory consolidation and distress adaptation across sleep.

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Acknowledgements

Y.C. discloses support for this work from the Cota Robles Fellowship. G.R.P. discloses support from the National Institute of Mental Health (R01 Grant MH60670). H.W.K. discloses support from the Brain Foundation Netherlands (DR-2018-00252). E.J.W.V.S. discloses support from the European Research Council (ERC-ADG-2014-671084 INSOMNIA and ERC-2021-ADG-101055383 OVERNIGHT) and from the Netherlands Organisation for Health Research and Development (ZonMw) project REMOVE 09120011910032. R.W. discloses support from the Sydney Local Health District and the Australian National Health and Medical Research Council (Investigator Grant GNT1196636).

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Author notes

  1. These authors contributed equally: Yesenia Cabrera, Karin J. Koymans.

Authors and Affiliations

  1. Department of Integrative Biology and Physiology, Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA

    Yesenia Cabrera & Gina R. Poe

  2. Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands

    Karin J. Koymans & Helmut W. Kessels

  3. Department of Synaptic Plasticity and Behaviour, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Society for Arts and Sciences, Amsterdam, Netherlands

    Helmut W. Kessels

  4. Department of Sleep and Cognition, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Society for Arts and Sciences, Amsterdam, Netherlands

    Eus J. W. Van Someren

  5. Department of Integrative Neurophysiology and Psychiatry, VU University, Amsterdam UMC, Amsterdam, Netherlands

    Eus J. W. Van Someren

  6. Center for Neurogenomics and Cognitive Research, VU University, Amsterdam UMC, Amsterdam, Netherlands

    Eus J. W. Van Someren

  7. Sleep and Circadian Research, Woolcock Institute of Medical Research, Macquarie University, Sydney, New South Wales, Australia

    Rick Wassing

  8. School of Psychological Sciences, Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia

    Rick Wassing

  9. Sydney Local Health District, Sydney, New South Wales, Australia

    Rick Wassing

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Cabrera, Y., Koymans, K.J., Poe, G.R. et al. Overnight neuronal plasticity and adaptation to emotional distress. Nat. Rev. Neurosci. 25, 253–271 (2024). https://doi.org/10.1038/s41583-024-00799-w

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