Learning-associated activation of nuclear MAPK, CREB and Elk-1, along withFos production, in the rat hippocampus after a one-trial avoidance learning: abolition by NMDA receptor blockade
M. Cammarota et al., Learning-associated activation of nuclear MAPK, CREB and Elk-1, along withFos production, in the rat hippocampus after a one-trial avoidance learning: abolition by NMDA receptor blockade, MOL BRAIN R, 76(1), 2000, pp. 36-46
It is widely accepted that the formation of long-term memory (LTM) requires
neuronal gene expression, protein synthesis and the remodeling of synaptic
contacts. From mollusk to mammals, the cAMP/PKA/CREB signaling pathway has
been shown to play a pivotal role in the establishment of LTM. More recent
ly, the MAPK cascade has been also involved in memory processing. Here, we
provide evidence for the participation of hippocampal PKA/CREB and MAPK/Elk
-1 pathways, via activation of NMDA receptors, in memory formation of a one
-trial avoidance learning in rats. Learning of this task is associated with
an activation of p44 and p42, MAPKs, CREB and Elk-1, along with an increas
e in the levels of the catalytic subunit of PKA and Fos protein in nuclear-
enriched hippocampal fractions. These changes were blocked by the immediate
posttraining intra-hippocampal infusion of APV, a selective blocker of glu
tamate NMDA receptors, which renders the animals amnesic for this task. Mor
eover, no changes were found in control-shocked animals. Thus, inhibitory a
voidance training in the rat is associated with an increase in the protein
product of an IEG, c-fos, which occurs concomitantly with the activation of
nuclear MAPK, CREB and Elk-1. NMDA receptors appear to be a necessary upst
ream step for the activation of these intracellular cascades during learnin
g. (C) 2000 Elsevier Science B.V. All rights reserved.