Hippocampal CaMKII Regulates the Consolidation of Recognition Memory

Abstract

Object recognition memory (ORM) is a hippocampus-dependent form of memory essential for distinguishing items and constructing episodic representations of the past. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine-specific protein kinase highly enriched in the hippocampal formation, where it acts as a memory-relevant calcium effector. We found that, in rats, training in an ORM inducing learning task rapidly increased CaMKII autophosphorylation in the CA1 region of the dorsal hippocampus. Moreover, early post-acquisition intra-dorsal CA1 injection of the substrate-competitive CaMKII inhibitor AIP impaired long-term ORM without affecting short-term ORM or previously consolidated ORMs. The amnesia induced by AIP was replicated by the calmodulin-competitive CaMKII inhibitor KN93, but not by the inactive analogues of either KN93 or AIP. Notably, these effects occurred regardless of the subject's sex and age or the time of day when learning took place. Together, our findings indicate that hippocampal CaMKII activity is necessary shortly after training for the normal consolidation of ORM.