Neurosteroid paradoxical enhancement of paired-pulse inhibition through paired-pulse facilitation of inhibitory circuits in dentate granule cells
Neuropharmacology. 2005-03-01; 48(4): 584-596
DOI: 10.1016/j.neuropharm.2004.11.014
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1. Neuropharmacology. 2005 Mar;48(4):584-96.
Neurosteroid paradoxical enhancement of paired-pulse inhibition through
paired-pulse facilitation of inhibitory circuits in dentate granule cells.
Thomas MJ(1), Mameli M, Carta M, Valenzuela CF, Li PK, Partridge LD.
Author information:
(1)Department of Neurosciences, University of New Mexico School of Medicine,
Albuquerque, NM 87131, USA.
Neurosteroids are produced in the brain independently of peripheral endocrine
glands to act locally in the nervous system. They exert potent promnesic effects
and play significant roles in mental health-related disorders. In part,
neurosteroids act by affecting ligand-gated ion channels and metabotropic
receptors through rapid non-genomic processes. We have previously demonstrated
that neurosteroids also affect synaptic transmission presynaptically in the CA1
region of the hippocampus. Here we describe the effects of the most abundant
neurosteroid in the rodent brain, pregnenolone sulfate (PregS), on signal
processing in the dentate subfield of the hippocampus. We show that PregS acts
presynaptically at low concentrations (300 nM) to enhance paired-pulse
facilitation (PPF) in perforant pathway terminals on dentate granule cells.
Similar effects were found with two steroid sulfatase inhibitors demonstrating a
potential contribution of endogenous steroids to dentate synaptic plasticity.
This enhanced presynaptic facilitation paradoxically increases paired-pulse
inhibition (PPI) at short interpulse intervals. Based on these data, a model of
dentate gyrus circuit interactions is proposed for the presynaptic action of
PregS on the filtering dynamics of the dentate subfield at frequencies similar to
those of the endogenous signals from the entorhinal cortex. These modeling
studies are consistent with experimental measurements demonstrating positive
modulation by PregS at low frequencies and negative modulation at high
frequencies. These studies show an important role for the presynaptic action of
neurosteroids in modulating input signals to the hippocampus.
DOI: 10.1016/j.neuropharm.2004.11.014
PMID: 15755486 [Indexed for MEDLINE]