CALCINEURIN AS A REGULATOR OF MEMORY FORMATION: REGULATION OF NF-κB SIGALLING PATHWAY

DE LA FUENTE V; FEDERMAN N; FUSTIÑANA MS; ZALCMAN G; ROMANO A

Munich

Congreso; 45th European Brain and Behaviour Society (EBBS) meeting; 2013

European Brain and Behaviour Society

Previous studies on synaptic signaling in neural plasticity support that synaptic strengthening is induced by altering the balance between protein kinases and protein phosphatases towards kinases activation. 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 suggests its role as a constraint in memory formation in different animal models, but there are few studies proposing which signaling pathways CaN indeed regulate. On the other hand, it is well known that the transcription factor NF-κB is a key mechanism for memory formation. In the present work we studied the effect of CaN inhibition in hippocampus during fear conditioning consolidation and -, for the first time at our knowledge - in reconsolidation, and assessed whether NF-κB signaling pathway is regulated by this phosphatase. We found that hippocampal CaN inhibition by means of FK506 administration improved contextual fear memory and if NF-κB was also inhibited by sulfasalazine intrahippocampal administration, facilitation of memory was not observed, suggesting that CaN exerts its negative regulation via NF-κB pathway. Regarding reconsolidation phase of memory, CaN inhibition before retrieval facilitates memory, and this facilitation is also dependent on NF-κB signaling. Our results propose a novel mechanism by which memories formation can be controlled by protein phosphatases.