Protein kinase C inhibitors eliminate hippocampal long-term potentiation

David M. Lovinger, Ka L. Wong, Kentaro Murakami, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Recent findings suggest that protein kinase C (PKC) regulates the persistence of long-term potentiation (LTP). To test the hypothesis that PKC inhibition would decrease persistence of potentiation we applied PKC inhibitors (mellitin, polymyxin B, H-7) by micropressure ejection to the intact hippocampus either before or after LTP induction. When inhibitor was given 15 min before LTP, initial potentiation was unaffected, yet responses decayed to baseline levels by 60 min after the onset of potentiation. PKC inhibitor treatment 10 min after LTP onset induced decay of responses to pre-LTP baseline levels within 50 min of ejection. Inhibitor applied 60 min after LTP onset induced substantial decay but to not baseline levels. Potentiation was unaffected by inhibitor treatment 4 h after the induction of LTP. Measurement of PKC subcellular distribution revealed that inhibitor significantly reduced the proportion of PKC associated with the membrane. These findings represent the first demonstration that PKC inhibitors prevent persistence of potentiation. They also suggest that PKC regulates the persistence of synaptic enhancement beginning after its onset, and that PKC's role decreases with time after the induction of enhancement.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalBrain research
Volume436
Issue number1
DOIs
StatePublished - Dec 8 1987

Keywords

  • Dentate gyrus
  • H-7
  • Mellitin
  • Perforant path
  • Polymyxin B
  • Protein phosphorylation
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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