TYROSINE KINASE IS REQUIRED FOR LONG-TERM DEPRESSION IN THE CEREBELLUM

Long-term depression (LTD) at the parallel fiber-Purkinje cell synapse in the cerebellum is a well-known example of synaptic plasticity. Alt hough LTD is thought to reflect an enduring loss of postsynaptic AMPA receptor sensitivity, the underlying mechanisms are unclear. Protein-t yrosine kinases (PTKs) are able to modulate ionotropic receptor functi on and are enriched in Purkinje cells. Using intracellular recording f rom Purkinje cells, it is shown that two structurally and mechanistica lly distinct PTK inhibitors, lavendustin A and herbimycin A, block LTD induced by pairing parallel fiber stimulation with postsynaptic Ca2spiking. Intracellular application of the protein kinase C (PKC) activ ator, (-)-indolactam V, consistently depressed parallel fiber-Purkinje cell EPSPs and occluded pairing-induced LTD. Herbimycin A nullified t he run-down produced by (-)-indolactam V. These data suggest that PTKs are necessary for LTD at the parallel fiber-Purkinje cell synapse and that PKC-induced synaptic depression requires PTK activity.