MAPK activation in the hippocampus in vivo is correlated with experimental setting

The mitogen-activated protein kinase (MAPK) pathway is an evolutionarily conserved signaling cascade involved in both synaptic plasticity and memory formation. Following our recent observation of translation regulation in taste learning and memory, we aimed to study MAPK-dependent translation regulation in long-term potentiation (LTP), a cellular model of learning and memory. We first analyzed ERK1/2 activation following high-frequency stimulation in the dentate gyrus (DG) of the hippocampus, in vivo. Surprisingly, our results indicate that the activation of both ERK2 and p38 was strongly affected by the order in which the DG was dissected out, but not by other experimental parameters. Specifically, we found that ERK2 and p38 phosphorylation were higher in the second than in the first dentate gyrus removed (up to 30 s apart). Similar results were obtained when we isolated the 'order of removal' factor by looking at MAPK phosphorylation in rats that had not undergone any electrophysiological procedure (i.e., naïve rats). This effect is so robust, that it probably masks the effect of LTP induction on MAPK activation. We suggest that some of the correlations found between MAPK activation and brain function in vivo may be due to cellular stress. In addition, careful experimental procedures and control are indispensable in the analysis of biochemical correlations of post-translation modifications that subserve both general neuronal function and synaptic plasticity.