Closed-loop brain stimulation augments fear extinction in male rats
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....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39546-7 |
| _version_ | 1797784490200793088 |
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| author | 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 Berényi |
| author_facet | 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 Berényi |
| author_sort | Rodrigo Ordoñez Sierra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T00:40:39Z |
| format | Article |
| id | doaj.art-6d10aa8b882e44f8b23463c86bb30464 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T00:40:39Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6d10aa8b882e44f8b23463c86bb304642023-07-09T11:18:51ZengNature PortfolioNature Communications2041-17232023-07-0114111410.1038/s41467-023-39546-7Closed-loop brain stimulation augments fear extinction in male ratsRodrigo Ordoñez Sierra0Lizeth Katherine Pedraza1Lívia Barcsai2Andrea Pejin3Qun Li4Gábor Kozák5Yuichi Takeuchi6Anett J. Nagy7Magor L. Lőrincz8Orrin Devinsky9György Buzsáki10Antal Berényi11MTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedDepartment of Neurology, NYU Langone Comprehensive Epilepsy Center, NYU Grossman School of MedicineNeuroscience Institute, New York UniversityMTA-SZTE ‘Momentum’ Oscillatory Neuronal Networks Research Group, Department of Physiology, University of SzegedAbstract 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.https://doi.org/10.1038/s41467-023-39546-7 |
| spellingShingle | 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 Berényi Closed-loop brain stimulation augments fear extinction in male rats Nature Communications |
| title | Closed-loop brain stimulation augments fear extinction in male rats |
| title_full | Closed-loop brain stimulation augments fear extinction in male rats |
| title_fullStr | Closed-loop brain stimulation augments fear extinction in male rats |
| title_full_unstemmed | Closed-loop brain stimulation augments fear extinction in male rats |
| title_short | Closed-loop brain stimulation augments fear extinction in male rats |
| title_sort | closed loop brain stimulation augments fear extinction in male rats |
| url | https://doi.org/10.1038/s41467-023-39546-7 |
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