Desregulación de ERK/MAPK, un posible mecanismo de acción en el deterioro cognitivo en un modelo de EA

FELD M

CABA

Congreso; XX Congreso Argentino de la Enfermedad de Alzheimer y otros trastornos relacionados; 2017

Historically, context-specific long term memory (LTM) in the crab Neohelice granulata consisted of 15 trials of an aversive stimulus with a 3-min inter-trial interval (ITI). Here, we describe a new protocol that allows LTM formation and expression 24h after a 2-trial training session using 45min-ITI (2t-LTM). We found that 2t-LTM is context-specific and sensitive to protein synthesis inhibitors both during consolidation and reconsolidation. Moreover, MEK-1 (extracellular signal-regulated kinase 1/2, ERK1/2, kinase) inhibitor administered between both training trials impaired 2t-LTM. The underlying hypothesis is that the first trial induces a context-specific activation of ERK pathway, enabling the formation of a LTM only when the second trial is presented 45 min later.Along this line, during the reconsolidation process ERK1/2 pathway may play a key role during memory trace stabilization. Using the inhibitory avoidance task in mice, we have recently reported that two foot-shock intensities revealed different activation kinetics of ERK1/2 after memory reactivation. We have also shown that hippocampal α7 nicotinic acetylcholine receptors (nAChRs) play a critical role in the reconsolidation processes depending on training intensity. Next, we determined that nAChRs are able to modulate ERK1/2. Therefore, we wanted to study whether differential ERK kinetics is a consequence of the activation/inhibition of same hippocampal (sub)areas or activation of different neuronal (sub)populations. We trained mice with two different foot-shock intensities and performed c-fos immunohistochemical stainings of the hippocampus at different times after memory reactivation. Our results help to understand molecular and cellular differences in memory stabilization between two different types of training.