A Protein Synthesis–Dependent Late Phase of Cerebellar Long-Term Depression

Synthesis of new protein has been shown to be required for establishment of a late phase in hippocampal long-term potentiation. Whether a similar requirement is needed to produce the late phase of long-term depression (LTD) remains to be determined. Application of transcription inhibitors or of the translation inhibitor anisomycin, immediately, but not 30 min after glutamate/depolarization conjunction, attenuated a late phase of cerebellar LTD in culture. LTD, produced in a perforated outside-out macropatch of Purkinje neuron dendrite, which lacks nuclear material, returned to baseline values with a time course paralleling that observed with protein synthesis inhibitors in intact cultured Purkinje neurons. These findings suggest that there is a distinct late phase of cerebellar LTD that is dependent upon postsynaptic protein synthesis.