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

Ahn Sohyun, David D. Ginty, David J. Linden

Research output: Contribution to journalArticlepeer-review

Abstract

Recently, it has been shown that cerebellar LTD has a late phase that may be blocked by protein synthesis inhibitors. To understand the mechanisms underlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particle- mediated transfection of cultured Purkinje neurons with an expression vector encoding a dominant inhibitory form of CREB resulted in a nearly complete blockade of the late phase. Kinases that activate CREB were inhibited, and LTD was assessed. Inhibition of PKA or the MAPK/RSK cascades were without effect on the late phase, while constructs designed to interfere with CaMKIV function attenuated the late phase. These results indicate that the activation of CaMKIV and CREB are necessary to establish a late phase of cerebellar LTD.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalNeuron
Volume23
Issue number3
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Neuroscience(all)

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