Bi. Kanterewicz et al., The extracellular signal-regulated kinase cascade is required for NMDA receptor-independent LTP in area CA1 but not area CA3 of the hippocampus, J NEUROSC, 20(9), 2000, pp. 3057-3066
Activation of extracellular signal-regulated kinase (ERK) has been shown to
be necessary for NMDA receptor-dependent long-term potentiation (LTP). We
studied the role of ERK in three forms of NMDA receptor-independent LTP: LT
P induced by very high-frequency stimulation (200 Hz-LTP), LTP induced by t
he K+ channel blocker tetraethylammonium (TEA) (TEA-LTP), and mossy fiber (
MF) LTP (MF-LTP). We found that ERK was activated in area CA1 after the ind
uction of both 200 Hz-LTP and TEA-LTP and that this activation required the
influx of Ca2+ through voltage-gated Ca2+ channels. Inhibition of the ERK
signaling cascade with either PD 098059 or U0126 prevented the induction of
both 200 Hz-LTP and TEA-LTP in area CA1. In contrast, neither PD 098059 no
r U0126 prevented MF-LTP in area CA3 induced by either brief or long trains
of high-frequency stimulation. U0126 also did not prevent forskolin-induce
d potentiation in area CA3. However, incubation of slices with forskolin, a
n activator of the cAMP-dependent protein kinase (PKA) cascade, did result
in increases in active ERK and cAMP response element-binding protein (CREB)
phosphorylation in area CA3. The forskolin-induced increase in active ERK
was inhibited by U0126, whereas the increase in CREB phosphorylation was no
t, which suggests that in area CA3 the PKA cascade is not coupled to CREB p
hosphorylation via ERK. Overall, our observations indicate that activation
of the ERK signaling cascade is necessary for NMDA receptor-independent LTP
in area CA1 but not in area CA3 and suggest a divergence in the signaling
cascades underlying NMDA receptor-independent LTP in these hippocampal subr
egions.