Home Blog of Signal Transduction Neuronal Signaling CaMK Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse

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Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse

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.

 

Comments:

It seems like you're discussing a detailed study that explores the role of hippocampal CaMKII (Ca2+/calmodulin-dependent protein kinase II) in fear extinction memory reconsolidation in rats. The study suggests that inhibiting CaMKII activity in the dorsal-CA1 region of the hippocampus after fear extinction memory recall impairs extinction and leads to the recovery of fear, mediated by GluN2B-NMDAR (N-methyl-D-aspartate receptor) activation.

This finding is intriguing as it highlights the importance of CaMKII in the reconsolidation of fear extinction memory. The inhibition of CaMKII seems to disrupt the process by which fear extinction is maintained and prevents the suppression of learned fear. This sheds light on potential mechanisms that regulate fear memory consolidation and extinction, offering insights into how specific molecular pathways could be targeted to modulate fear-related behaviors.

Understanding these pathways and the role of proteins like CaMKII in memory processes could potentially lead to the development of targeted therapies or interventions for conditions involving fear-related memories, such as post-traumatic stress disorder (PTSD) or specific phobias. However, further research would likely be necessary to fully elucidate the implications and potential applications of these findings in clinical settings.

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S6507 KN-92 phosphate KN-92 is an inactive derivative of KN-93, the selective inhibitor of Ca2+/calmodulin-dependent kinase type II (CaMKII).

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CaMK