A new form of cerebellar long-term potentiation is postsynaptic and depends on nitric oxide but not cAMP.

Long-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell synapses must be balanced by long-term potentiation (LTP) to prevent saturation and allow reversal of motor learning. The only previously analyzed form of cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not nitric oxide. It is a poor candidate to reverse LTD because it is presynaptically expressed whereas LTD is postsynaptic. We now characterize a new form of LTP induced by 1 Hz PF stimulation for at least 300 s. This LTP is postsynaptically expressed, enhanced by chelating postsynaptic Ca(2+), and depends on nitric oxide but not cAMP or cGMP, making it a plausible anti-Hebbian counterpart to Hebbian LTD.