Neurosteroid paradoxical enhancement of paired-pulse inhibition through paired-pulse facilitation of inhibitory circuits in dentate granule cells.

Details

Serval ID
serval:BIB_7EEC78537F74
Type
Article: article from journal or magazin.
Collection
Publications
Title
Neurosteroid paradoxical enhancement of paired-pulse inhibition through paired-pulse facilitation of inhibitory circuits in dentate granule cells.
Journal
Neuropharmacology
Author(s)
Thomas M.J., Mameli M., Carta M., Valenzuela C.F., Li P.K., Partridge L.D.
ISSN
0028-3908 (Print)
ISSN-L
0028-3908
Publication state
Published
Issued date
03/2005
Peer-reviewed
Oui
Volume
48
Number
4
Pages
584-596
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
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.

Keywords
Animals, Dentate Gyrus/drug effects, Dentate Gyrus/physiology, Dose-Response Relationship, Drug, Male, Nerve Net/drug effects, Nerve Net/physiology, Neural Inhibition/drug effects, Neural Inhibition/physiology, Neurotransmitter Agents/pharmacology, Pregnenolone/pharmacology, Rats, Rats, Sprague-Dawley, Synaptic Transmission/drug effects, Synaptic Transmission/physiology
Pubmed
Web of science
Create date
03/02/2017 11:24
Last modification date
20/08/2019 14:39
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