Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation

Mitogen-activated protein kinase (MAPK) cascade classically is thought to b e involved in cellular transformation, including proliferation and differen tiation. Recent behavioral studies suggest that MAPK may also have a role i n learning and memory. Long-term potentiation (LTP), a candidate mechanism for learning and memory, has at least two distinct temporal phases: an earl y phase (E-LTP) which lasts for 1-2 h and a late phase (L-LTP) which can pe rsist greater than or equal to 3 h, Here, we report that PD 098059, a selec tive inhibitor of MAPK cascade, attenuates L-LTP induced by bath applicatio n of forskolin without affecting basal synaptic transmission. This effect w as mimicked by direct injection of animals with MAPK antisense oligonucleot ide into the hippocampal CA1 region. MAPK activity measured by using a synt hetic peptide corresponding to the sequence surrounding the major site of p hosphorylation of the myelin-basic protein by MAPK was enhanced by forskoli n, The same antisense treatment also completely inhibited the increased MAP K activity. These results demonstrate an involvement of MAPK in the inducti on of L-LTP in the hippocampal CA1 neurons.