A late phase of cerebellar long-term depression requires activation of CaMKIV and CREB

Recently, it has been shown that cerebellar LTD has a late phase that may b e blocked by protein synthesis inhibitors. To understand the mechanisms und erlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particl e-mediated transfection of cultured Purkinje neurons with an expression vec tor encoding a dominant inhibitory form of CREB resulted in a nearly comple te blockade of the late phase. Kinases that activate CREB were inhibited, a nd LTD was assessed. Inhibition of PKA or the MAPK/RSK cascades were withou t effect on the late phase, while constructs designed to interfere with CaM KIV function attenuated the late phase. These results indicate that the act ivation of CaMKIV and ORES are necessary to establish a late phase of cereb ellar LTD.