MOLECULAR MECHANISMS IN THE SWITCH BETWEEN RECONSOLIDATION AND EXTINCTION OF FEAR MEMORY

VERÓNICA DE LA FUENTE; ARTURO ROMANO

Huerta Grande, Córdoba

Congreso; First Joint Meeting of the Argentine Society for Neuroscience; 2009

Sociedad Argentina de Investigación en Neurociencias (SAN)

When contextual associative memory is reactivated by context re-exposure, two apparently competing processes, reconsolidation or extinction, may be induced. A brief re-exposure to the training context induces memory reconsolidation, while a prolonged re-exposure induces the inhibition of the conditioned response, a process known as memory extinction. Two main hypotheses, not mutually exclusive, intend to explain memory extinction. The first one implies a pathway that inhibits the original memory circuit. The other implies a weakening of the original trace. Using contextual fear conditioning in mice, we studied the role of transcription regulation in reconsolidation and extinction of memory. We observed that hippocampal NF-kB activation is necessary for reconsolidation, but not for extinction. Besides, hippocampal calcineurin phosphatase (CaN) activity is required for the formation of extinction memory but not for reconsolidation of the original memory trace. Considering that NF-kB is activated by IkB phosphorilation and PKA kinases, we asked whether CaN is dephosphorilating and thus inhibiting NF-kB during extinction. Inhibition of CaN in hippocampus increased hippocampal NF-kB activity and impeded memory extinction. Besides, CaN is known to activate another transcription factor, NFAT. We observed that hippocampal inhibition of NFATc4 impeded extinction, whereas no effects where observed in reconsolidation. Thus, our results suggest that CaN inhibition of NF-kB and activation of NFAT are involved in the regulation of gene expression that determines the switch between memory reconsolidation and extinction. These results, also supports the hypothesis that the extinction of memory implies a weakening of the original trace.