A role for the basal forebrain cholinergic system in estrogen-induced disinhibition of hippocampal pyramidal cells

Charles N. Rudick, Robert B. Gibbs, Catherine S. Woolley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Estrogen transiently hippocampal CA1 pyramidal cells in adult female rats and prolongs the decay time of IPSCs in these cells. Estrogen-induced changes in synaptic inhibition are likely to be causally related to subsequent enhancements in excitatory synaptic function in CA1 pyramidal cells. Currently, it is unknown how or on what cells estrogen acts to regulate synaptic inhibition in the hippocampus. We used whole-cell voltage-clamp recording of synaptically evoked IPSCs, spontaneous IPSCs, and miniature IPSCs in CA1 pyramidal cells to evaluate estrogen-induced changes in synaptic inhibition in ovariectomized rats that either were pretreated with the estrogen receptor (ER) antagonist tamoxifen or in which basal forebrain cholinergic neurons were eliminated by previous infusion of 192IgG-saporin toxin into the medial septum. We found that estrogen-induced disinhibition and prolongation of IPSCs are entirely dependent on a tamoxifen-sensitive ER. Estrogen-induced disinhibition is partially dependent on basal forebrain cholinergic neurons, but the prolongation of IPSCs is not at all dependent on these cells. Paired-pulse experiments and recordings of action potential-related spontaneous IPSCs suggest that estrogen-induced disinhibition is associated with a decrease in probability of release at GABAergic synapses, which decreases the amplitude of IPSCs produced by inhibitory neuron action potentials. Our findings lend novel insights into estrogen regulation of inhibitory synapses in the hippocampus and point to estrogen action on basal forebrain cholinergic neurons as critically involved in mediating the effects of estrogen in the hippocampus.

Original languageEnglish (US)
Pages (from-to)4479-4490
Number of pages12
JournalJournal of Neuroscience
Volume23
Issue number11
DOIs
StatePublished - Jun 1 2003

Keywords

  • 192IgG-saporin
  • CA1
  • ChAT
  • Estradiol
  • GABA
  • IPSCs
  • Tamoxifen

ASJC Scopus subject areas

  • Neuroscience(all)

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