학술논문
Closed-loop brain stimulation augments fear extinction in male rats.
Document Type
Academic Journal
Author
Sierra RO; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Pedraza LK; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Barcsai L; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; HCEMM-SZTE Magnetotherapeutics Research Group, University of Szeged, Szeged, 6720, Hungary.; Neunos Inc, Boston, MA, 02108, USA.; Pejin A; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; HCEMM-SZTE Magnetotherapeutics Research Group, University of Szeged, Szeged, 6720, Hungary.; Neunos Inc, Boston, MA, 02108, USA.; Li Q; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Kozák G; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Takeuchi Y; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Department of Biopharmaceutical Sciences and Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.; Nagy AJ; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; HCEMM-SZTE Magnetotherapeutics Research Group, University of Szeged, Szeged, 6720, Hungary.; Neunos Inc, Boston, MA, 02108, USA.; Lőrincz ML; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary.; Department of Physiology, Anatomy and Neuroscience, Faculty of Sciences University of Szeged, Szeged, 6726, Hungary.; Neuroscience Division, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.; Devinsky O; Department of Neurology, NYU Langone Comprehensive Epilepsy Center, NYU Grossman School of Medicine, New York, NY, 10016, USA.; Buzsáki G; Neuroscience Institute, New York University, New York, NY, 10016, USA.; Center for Neural Science, New York University, New York, NY, 10016, USA.; Berényi A; MTA-SZTE 'Momentum' Oscillatory Neuronal Networks Research Group, Department of Physiology, University of Szeged, Szeged, 6720, Hungary. drberenyi@gmail.com.; HCEMM-SZTE Magnetotherapeutics Research Group, University of Szeged, Szeged, 6720, Hungary. drberenyi@gmail.com.; Neunos Inc, Boston, MA, 02108, USA. drberenyi@gmail.com.; Neuroscience Institute, New York University, New York, NY, 10016, USA. drberenyi@gmail.com.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. The Author(s).)
(© 2023. The Author(s).)