Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse
Abstract Hippocampal GluN2B subunit-containing NMDAR (GluN2B-NMDAR) activation during recall destabilizes fear extinction memory, which must undergo brain-derived neurotrophic factor (BDNF)-dependent reconsolidation to persist. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr protei...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48454-1 |
| _version_ | 1827590593648263168 |
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| author | Andressa Radiske Carla Miranda de Castro Janine I. Rossato Maria Carolina Gonzalez Martín Cammarota |
| author_facet | Andressa Radiske Carla Miranda de Castro Janine I. Rossato Maria Carolina Gonzalez Martín Cammarota |
| author_sort | Andressa Radiske |
| collection | DOAJ |
| description | Abstract Hippocampal GluN2B subunit-containing NMDAR (GluN2B-NMDAR) activation during recall destabilizes fear extinction memory, which must undergo brain-derived neurotrophic factor (BDNF)-dependent reconsolidation to persist. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr protein kinase essential for hippocampus-dependent memory processing that acts downstream GluN2B-NMDAR and controls BDNF expression, but its participation in fear extinction memory reconsolidation has not yet been studied. Using a combination of pharmacological and behavioral tools, we found that in adult male Wistar rats, intra dorsal-CA1 administration of the CaMKII inhibitors autocamtide-2-related inhibitory peptide (AIP) and KN-93, but not of their inactive analogs scrambled AIP and KN-92, after fear extinction memory recall impaired extinction and caused GluN2B-NMDAR-dependent recovery of fear. Our results indicate that hippocampal CaMKII is necessary for fear extinction reconsolidation, and suggest that modulation of its activity around the time of recall controls the inhibition that extinction exerts on learned fear. |
| first_indexed | 2024-03-09T01:19:01Z |
| format | Article |
| id | doaj.art-dcb7bd3e27514d82b127ccc3dd4e13ea |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T01:19:01Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dcb7bd3e27514d82b127ccc3dd4e13ea2023-12-10T12:17:45ZengNature PortfolioScientific Reports2045-23222023-12-011311610.1038/s41598-023-48454-1Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapseAndressa Radiske0Carla Miranda de Castro1Janine I. Rossato2Maria Carolina Gonzalez3Martín Cammarota4Memory Research Laboratory - Brain Institute, Federal University of Rio Grande do NorteMemory Research Laboratory - Brain Institute, Federal University of Rio Grande do NorteMemory Research Laboratory - Brain Institute, Federal University of Rio Grande do NorteMemory Research Laboratory - Brain Institute, Federal University of Rio Grande do NorteMemory Research Laboratory - Brain Institute, Federal University of Rio Grande do NorteAbstract Hippocampal GluN2B subunit-containing NMDAR (GluN2B-NMDAR) activation during recall destabilizes fear extinction memory, which must undergo brain-derived neurotrophic factor (BDNF)-dependent reconsolidation to persist. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a Ser/Thr protein kinase essential for hippocampus-dependent memory processing that acts downstream GluN2B-NMDAR and controls BDNF expression, but its participation in fear extinction memory reconsolidation has not yet been studied. Using a combination of pharmacological and behavioral tools, we found that in adult male Wistar rats, intra dorsal-CA1 administration of the CaMKII inhibitors autocamtide-2-related inhibitory peptide (AIP) and KN-93, but not of their inactive analogs scrambled AIP and KN-92, after fear extinction memory recall impaired extinction and caused GluN2B-NMDAR-dependent recovery of fear. Our results indicate that hippocampal CaMKII is necessary for fear extinction reconsolidation, and suggest that modulation of its activity around the time of recall controls the inhibition that extinction exerts on learned fear.https://doi.org/10.1038/s41598-023-48454-1 |
| spellingShingle | Andressa Radiske Carla Miranda de Castro Janine I. Rossato Maria Carolina Gonzalez Martín Cammarota Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse Scientific Reports |
| title | Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse |
| title_full | Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse |
| title_fullStr | Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse |
| title_full_unstemmed | Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse |
| title_short | Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse |
| title_sort | hippocampal camkii inhibition induces reactivation dependent amnesia for extinction memory and causes fear relapse |
| url | https://doi.org/10.1038/s41598-023-48454-1 |
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