Persistent caMKII activation mediates learning-induced long-lasting enhancement of synaptic inhibition

Sourav Ghosh, Iris Reuveni, Raphael Lamprecht, Edi Barkai

Research output: Contribution to journalArticlepeer-review

Abstract

Training rats in a particularly difficult olfactory-discrimination task results in acquisition of high skill to perform the task superbly, termed “rule learning” or “learning set.” Such complex learning results in enhanced intrinsic neuronal excitability of piriform cortex pyramidal neurons, and in their excitatory synaptic interconnections. These changes, while subserving memory maintenance, must be counterbalanced by modifications that prevent overspreading of activity and uncontrolled synaptic strengthening. Indeed, we have previously shown that the average amplitude of GABAA-mediated miniature IPSCs (mIPSCs) in these neurons is enhanced for several days after learning, an enhancement mediated via a postsynaptic mechanism. To unravel the molecular mechanism of this long-term inhibition enhancement,wetested the roleof key second-messenger systemsinmaintaining such long-lasting modulation. The calcium/ calmodulin-dependent kinase II (CaMKII) blocker, KN93, significantly reduced the average mIPSC amplitude in neurons from trained rats onlytothe average pretraininglevel.Asimilar effect was obtainedbythe CaMKII peptideinhibitor, tatCN21. Suchreductionresulted from decreased single-channel conductance and not in the number of activated channels. The PKC inhibitor, GF109203X, reduced the average mIPSC amplitude in neurons from naive, pseudo-trained, and trained animals, and the difference between the trained and control groups remained. Such reduction resulted froma decreasein the number of activated channels. The PKA inhibitor H89 dihydro-chloride did not affect the average mIPSC amplitude in neurons from any of the three groups. We conclude that learning-induced enhancement of GABAA-mediated synaptic inhibition is maintained by persistent CaMKII activation.

Original languageEnglish
Pages (from-to)128-139
Number of pages12
JournalJournal of Neuroscience
Volume35
Issue number1
DOIs
StatePublished - 7 Jan 2015

Bibliographical note

Publisher Copyright:
© 2015 the authors.

Keywords

  • Olfactory learning
  • Piriform cortex
  • Pyramidal neurons
  • Second messenger
  • Synaptic inhibition

ASJC Scopus subject areas

  • Neuroscience (all)

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