IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v586y2020i7827d10.1038_s41586-020-2731-9.html
   My bibliography  Save this article

Deep posteromedial cortical rhythm in dissociation

Author

Listed:
  • Sam Vesuna

    (Stanford University)

  • Isaac V. Kauvar

    (Stanford University
    Stanford University)

  • Ethan Richman

    (Stanford University)

  • Felicity Gore

    (Stanford University
    Stanford University)

  • Tomiko Oskotsky

    (Stanford University
    Stanford University)

  • Clara Sava-Segal

    (Stanford University)

  • Liqun Luo

    (Stanford University
    Stanford University)

  • Robert C. Malenka

    (Stanford University)

  • Jaimie M. Henderson

    (Stanford University)

  • Paul Nuyujukian

    (Stanford University
    Stanford University
    Stanford University)

  • Josef Parvizi

    (Stanford University)

  • Karl Deisseroth

    (Stanford University
    Stanford University
    Stanford University)

Abstract

Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1–12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed—including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.

Suggested Citation

  • Sam Vesuna & Isaac V. Kauvar & Ethan Richman & Felicity Gore & Tomiko Oskotsky & Clara Sava-Segal & Liqun Luo & Robert C. Malenka & Jaimie M. Henderson & Paul Nuyujukian & Josef Parvizi & Karl Deisser, 2020. "Deep posteromedial cortical rhythm in dissociation," Nature, Nature, vol. 586(7827), pages 87-94, October.
  • Handle: RePEc:nat:nature:v:586:y:2020:i:7827:d:10.1038_s41586-020-2731-9
    DOI: 10.1038/s41586-020-2731-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-2731-9
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-020-2731-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Laura M. Hack & Xue Zhang & Boris D. Heifets & Trisha Suppes & Peter J. Roessel & Jerome A. Yesavage & Nancy J. Gray & Rachel Hilton & Claire Bertrand & Carolyn I. Rodriguez & Karl Deisseroth & Brian , 2023. "Ketamine’s acute effects on negative brain states are mediated through distinct altered states of consciousness in humans," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Francis Kei Masuda & Emily A. Aery Jones & Yanjun Sun & Lisa M. Giocomo, 2023. "Ketamine evoked disruption of entorhinal and hippocampal spatial maps," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Ahmad Mayeli & Obada Al Zoubi & Evan J. White & Sheridan Chappelle & Rayus Kuplicki & Alexa Morton & Jaimee Bruce & Ryan Smith & Justin S. Feinstein & Jerzy Bodurka & Martin P. Paulus & Sahib S. Khals, 2023. "Parieto-occipital ERP indicators of gut mechanosensation in humans," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Fangyun Tian & Laura D. Lewis & David W. Zhou & Gustavo A. Balanza & Angelique C. Paulk & Rina Zelmann & Noam Peled & Daniel Soper & Laura A. Santa Cruz Mercado & Robert A. Peterfreund & Linda S. Agli, 2023. "Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Ziyue Wang & Xiang Fei & Xiaotong Liu & Yanjie Wang & Yue Hu & Wanling Peng & Ying-wei Wang & Siyu Zhang & Min Xu, 2022. "REM sleep is associated with distinct global cortical dynamics and controlled by occipital cortex," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:586:y:2020:i:7827:d:10.1038_s41586-020-2731-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.