A novel role for extracellular signal-regulated kinase in maintaining long-term memory-relevant excitability changes

Sivan Ida Cohen-Matsliah, Inbar Brosh, Kobi Rosenblum, Edi Barkai

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Pyramidal neurons in the piriform cortex from olfactory-discrimination- trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the postburst afterhyperpolarization (AHP), which is generated by repetitive spike firing. AHP reduction is attributable to decreased conductance of a calcium-dependent potassium current, the sIAHP. We have previously shown that such learning-induced AHP reduction is maintained by PKC activation. However, the molecular machinery underlying such long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the extracellular signal-regulated kinase I/II (ERKI/II) pathway, which is known to be crucial in learning, memory, and synaptic plasticity processes, is instrumental for the long-term maintenance of learning-induced AHP reduction. PD98059 or UO126, which selectively block MEK, the upstream kinase of ERK, increased the AHP in neurons from trained rats but not in neurons from naive and pseudo-trained rats. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls were abolished. This effect was not mediated by modulation of basic membrane properties. In accordance with its effect on neuronal excitability, the level of activated ERK in the membranal fraction was significantly higher in piriform cortex samples taken from trained rats. In addition, the PKC activator OAG (1-oleoyl-20acety-sn-glycerol), which was shown to reduce the AHP in neurons from control rats, had no effect on these neurons in the presence of PD98059. Our data show that ERK has a key role in maintaining long-lasting learning-induced enhancement of neuronal excitability.

Original languageEnglish
Pages (from-to)12584-12589
Number of pages6
JournalJournal of Neuroscience
Issue number46
StatePublished - 14 Nov 2007
Externally publishedYes


  • ERK
  • Neuronal excitability
  • Olfactory learning
  • Piriform cortex
  • Postburst AHP
  • Pyramidal neurons

ASJC Scopus subject areas

  • General Neuroscience


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