Metrifonate increases neuronal excitability in CA1 pyramidal neurons from both young and aging rabbit hippocampus

Matthew M. Oh, John M. Power, Lucien T. Thompson, Pamela L. Moriearty, John F. Disterhoft*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The effects of metrifonate, a second generation cholinesterase inhibitor, were examined on CA1 pyramidal neurons from hippocampal slices of young and aging rabbits using current-clamp, intracellular recording techniques. Bath perfusion of metrifonate (10-200 μM) dose-dependently decreased both postburst afterhyperpolarization (AHP) and spike frequency adaptation (accommodation) in neurons from young and aging rabbits (AHP: p < 0.002, young; p < 0.050, aging; accommodation: p < 0.024, young; p < 0.001, aging). These reductions were mediated by muscarinic cholinergic transmission, because they were blocked by addition of atropine (1 μM) to the perfusate. The effects of chronic metrifonate treatment (12 mg/kg for 3 weeks) on CA1 neurons of aging rabbits were also examined ex vivo. Neurons from aging rabbits chronically treated with metrifonate had significantly reduced spike, frequency accommodation, compared with vehicle-treated rabbits. Chronic metrifonate treatment did not result in a desensitization to metrifonate ex vivo, because bath perfusion of metrifonate (50 μM) significantly decreased the AHP and accommodation in neurons from both chronically metrifonate- and vehicle-treated aging rabbits. We propose that the facilitating effect of chronic metrifonate treatment on acquisition of hippocampus-dependent tasks such as trace eyeblink conditioning by aging subjects may be caused by this increased excitability of CA1 pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)1814-1823
Number of pages10
JournalJournal of Neuroscience
Volume19
Issue number5
DOIs
StatePublished - Mar 1 1999

Keywords

  • Afterhyperpolarization
  • Aging
  • Atropine
  • Carbachol
  • Cholinesterase inhibitor
  • Eserine
  • Hippocampal slice
  • Metrifonate
  • Rabbits
  • Spike frequency adaptation

ASJC Scopus subject areas

  • Neuroscience(all)

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