A unique role of protein phosphatases in cerebellar long-term depression.

In order to investigate phosphorylation-dephosphorylation processes underlying long-term depression (LTD) in cerebellar Purkinje cells, the protein phosphatase inhibitors calyculin A and microcystein-LR were applied to Purkinje cells in guinea pig cerebellar slices either by bath application or by intracellular pressure injection. Under the influence of these protein phosphatase inhibitors, excitatory post-synaptic potentials evoked by stimulation of parallel fibres exhibited marked depression which developed at a rate dependent on the rate of parallel fibre stimulation. The protein phosphatase inhibitors thus substitute climbing fibre signals which induce LTD when combined with parallel fibre signals. Peculiarly, this is opposite to the effect in pyramidal cells, where protein phosphatase inhibitors block LTD.