Involvement of δCalcium/calmodulin-dependent protein kinase II in persistent forms of memory

GISELA ZALCMAN; NOEL FEDERMAN; ANA FISZBEIN; ARTURO ROMANO

Chicago

Congreso; 45th Society For Neuroscience Annual Meeting; 2015

Calcium/calmodulin-dependent protein kinase II (CaMKII) is an abundant synaptic signaling molecule that is essential for both memory formation and synaptic potentiation. In mammals, CaMKII exists in multiple isoforms that are the product of four closely related genes: α, β, γ, and δ. Little information is available on the role of the δCaMKII in memory processes. In a previous study, we showed that Camk2d gene promoter is acetylated in the mouse hippocampus one hour after strong novel object recognition (NOR) training and that its mRNA levels were specifically induced 3h post-training. Strong training induces long-term-memory (LTM) formation, which can be assessed up-to 7 days after training. In the present work, we carried out experiments aimed at determining the epigenetic regulation, expression and role of CamK2d on recognition memory. In the first place, we studied the Camk2d promoter and found there was nucleosome remodeling during NOR memory consolidation and 7 days after NOR training. Secondly, we measured δCamKII mRNA expression outside the memory consolidation window, more specifically 24 hs and 7 days after training, and we found that mRNA expression levels for animals trained with a strong protocol were significantly increased when compared to a non-trained control group at both time points. Finally, to study the requirement of δCaMKII in recognition memory we knocked down δCaMKII expression with an oligodeoxynucleotide antisense to its mRNA 3 hs after strong training and tested the memory effect 24hs and 7days afterwards. We found that NOR memory was intact 24hs after training but it was impaired when assessed on day 7, indicating that δCamKII knock-down during memory consolidation specifically affects persistent forms of recognition memories. Altogether, our results support a key role for δCaMKII isoform in persistent forms of memory and suggest that Camk2d may have a sustained expression throughout the ?lifetime? of this kind of memory. Furthermore, this is the first work that provides insight information about nucleosome remodeling during memory formation and maintenance.