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Closed-loop brain stimulation augments fear extinction in male rats

Author

Listed:
  • Rodrigo Ordoñez Sierra

    (University of Szeged)

  • Lizeth Katherine Pedraza

    (University of Szeged)

  • Lívia Barcsai

    (University of Szeged
    University of Szeged
    Neunos Inc)

  • Andrea Pejin

    (University of Szeged
    University of Szeged
    Neunos Inc)

  • Qun Li

    (University of Szeged)

  • Gábor Kozák

    (University of Szeged)

  • Yuichi Takeuchi

    (University of Szeged
    Hokkaido University)

  • Anett J. Nagy

    (University of Szeged
    University of Szeged
    Neunos Inc)

  • Magor L. Lőrincz

    (University of Szeged
    Faculty of Sciences University of Szeged
    Cardiff University)

  • Orrin Devinsky

    (NYU Grossman School of Medicine)

  • György Buzsáki

    (New York University
    New York University)

  • Antal Berényi

    (University of Szeged
    University of Szeged
    Neunos Inc
    New York University)

Abstract

Dysregulated fear reactions can result from maladaptive processing of trauma-related memories. In post-traumatic stress disorder (PTSD) and other psychiatric disorders, dysfunctional extinction learning prevents discretization of trauma-related memory engrams and generalizes fear responses. Although PTSD may be viewed as a memory-based disorder, no approved treatments target pathological fear memory processing. Hippocampal sharp wave-ripples (SWRs) and concurrent neocortical oscillations are scaffolds to consolidate contextual memory, but their role during fear processing remains poorly understood. Here, we show that closed-loop, SWR triggered neuromodulation of the medial forebrain bundle (MFB) can enhance fear extinction consolidation in male rats. The modified fear memories became resistant to induced recall (i.e., ‘renewal’ and ‘reinstatement’) and did not reemerge spontaneously. These effects were mediated by D2 receptor signaling-induced synaptic remodeling in the basolateral amygdala. Our results demonstrate that SWR-triggered closed-loop stimulation of the MFB reward system enhances extinction of fearful memories and reducing fear expression across different contexts and preventing excessive and persistent fear responses. These findings highlight the potential of neuromodulation to augment extinction learning and provide a new avenue to develop treatments for anxiety disorders.

Suggested Citation

  • Rodrigo Ordoñez Sierra & Lizeth Katherine Pedraza & Lívia Barcsai & Andrea Pejin & Qun Li & Gábor Kozák & Yuichi Takeuchi & Anett J. Nagy & Magor L. Lőrincz & Orrin Devinsky & György Buzsáki & Antal B, 2023. "Closed-loop brain stimulation augments fear extinction in male rats," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39546-7
    DOI: 10.1038/s41467-023-39546-7
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