ACTIVATION OF P42 MITOGEN-ACTIVATED PROTEIN-KINASE IN HIPPOCAMPAL LONG-TERM POTENTIATION

Although classically studied as regulators of cell proliferation and d ifferentiation, mitogen-activated protein kinases (MAPKs) are highly e xpressed in post-mitotic neurons of the adult nervous system. We have begun investigating the potential role of MAPKs in the regulation of s ynaptic plasticity in mature neurons. In particular, we have studied t he regulation of two MAPK isoforms, p44 and p42 MAPK, in hippocampal l ong term potentiation (LTP), a system widely studied as a model for th e cellular basis of learning and memory. We have found that p42 MAPK, but not p44 MAPK, is activated in area CA1 following direct stimulatio n of two required components of the LTP induction cascades: protein ki nase C and the N-methyl-D-aspartate (NMDA) subtype of glutamate recept or. Furthermore, we have demonstrated that p42 MAPK, but not p44 MAPK, is activated in area CA1 in response to LTP-inducing high frequency s timulation and that this activation requires NMDA receptor stimulation . These data demonstrate that p42 MAPK can be regulated in an activity -dependent manner in the hippocampus and identify it as a potential co mponent of the LTP induction cascades in area CA1. Such observations s uggest that p42 MAPK might be an important regulator of synaptic plast icity in post-mitotic neurons.