Calcineurin phosphatase as a memory constrain in consolidation and reconsolidation of fear memory.

DE LA FUENTE, VERÓNICA; FEDERMAN, NOEL; FUSTIÑANA, MARIA SOL; ROMANO, ARTURO

Washington

Congreso; SfN Meeting 2011; 2011

Society for Neuroscience

Many studies on synaptic signaling in neural plasticity support that synaptic strengthening is induced by altering the balance between protein kinases and protein phosphatases towards the side of the kinases. Conversely, synaptic depression is mediated by phosphatase activation. The phosphatase calcineurin CaN was particularly studied due to the fact that it is activated directly by Ca2+ - Calmodulin signals and that it is highly present in synaptic spines. Some studies using CaN KO mice support its role as a memory constrain in consolidation in different paradigms.  In our recent work, we have described a molecular switch in the hippocampus that directs memory towards either reconsolidation or extinction. According to that model, a brief re-exposure to the training context activates the transcription factor NF-kB and such activation is necessary for reconsolidation to take place. If the re-exposure is longer, CaN is activated, impeding NF-kB activation and, at the same time, induces nuclear translocation of the transcription factor NFAT –a downstream CaN target- leading to extinction of memory. These findings represent the first insight into the molecular mechanisms that determine memory reprocessing after retrieval. They also support the idea that the balance between phosphorylation and dephosphorylation plays a key role in the point of decision between reconsolidation and extinction. In light of these results, in the present work we studied the effect of CaN and NFAT pharmacological inhibition in consolidation and reconsolidation. We found that hippocampal CaN inhibition (by means of FK506 administration), but not hippocampal NFAT inhibition, improved contextual fear memory. The FK506-induced memory enhancement correlated with an increment in the activity of NF-kB. Similar results were obtained in reconsolidation. This results rule out a possible involvement of CaN in the process of labilization required for memory reconsolidation and strengthen the role of CaN function as a memory constrain in both consolidation and reconsolidation.