B-raf is a crucial player within the ERK/MAPK signaling pathway. In the CNS, B-raf has been implicated in neuronal differentiation, long-term memory and major depression. Mice with forebrain neuron-specific B-raf knockout show behavioral deficits in spatial learning tasks and impaired long-term potentiation in the hippocampus (Chen et al., J Neurosci Res 83:28–38, 2006). To elucidate the mechanism(s) underlying diminished synaptic plasticity in B-raf-deficient mice, we performed whole-cell recordings from CA1 pyramidal cells in hippocampal slices of control and B-raf knockout mice. As a first piece of evidence, we found that the NMDA/AMPA ratio of excitatory postsynaptic currents (EPSCs) was significantly reduced in B-raf mutants, which would at least partially account for their impaired LTP. We then examined apamin-sensitive, small-conductance Ca²⁺-activated K⁺ (SK) channels, which have been reported to modulate hippocampal LTP, learning and memory (Hammond et al., J Neurosci 26:1844–1853, 2006). To determine, whether B-raf-dependent signaling has an impact on SK current, we examined the effect of the SK channel blocker apamin (125 nM) in control and B-raf-deficient neurons. We used the apamin-sensitive tail current mediating the medium afterhyperpolarization (mAHP) after a strong depolarizing event as an indication of SK current and found indeed a significantly stronger SK current response in B-raf-deficient CA1 neurons compared to control cells. Our data suggest that ERK-MAPK signaling readjusts the delicate balance between NMDA receptors and SK channels to promote synaptic plasticity and facilitate hippocampal learning and memory.