Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus

Research output: Contribution to journalArticle

Abstract

Neurosteroids are potent allosteric modulators of GABAA receptors (GABAARs). Although the effects of exogenous neurosteroids on GABAAR function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB). Here, the effects of acute blockade of neurosteroidogenesis by the 5α-reductase inhibitor finasteride on phasic and tonic GABAAR-mediated currents were examined in nRT and VB of mice. In nRT, finasteride altered the decay and amplitude, but not the frequency, of phasic currents, with no effect on tonic inhibition. In VB neurons, by contrast, finasteride reduced both the size and frequency of phasic currents, and also reduced the degree of tonic inhibition. These studies thus provide novel evidence for endogenous modulation of GABAAR function by 5α-reduced neurosteroids in the mature thalamus.

Original languageEnglish (US)
Article numbere22144
JournalSynapse
DOIs
StateAccepted/In press - Jan 1 2019

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GABA-A Receptors
Finasteride
Thalamus
Neurotransmitter Agents
Oxidoreductases
3-Hydroxysteroid Dehydrogenases
Thalamic Nuclei
Neurons
Enzymes

Keywords

  • finasteride
  • GABA
  • neurosteroid
  • thalamus
  • tonic inhibition

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

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title = "Nucleus-specific modulation of phasic and tonic inhibition by endogenous neurosteroidogenesis in the murine thalamus",
abstract = "Neurosteroids are potent allosteric modulators of GABAA receptors (GABAARs). Although the effects of exogenous neurosteroids on GABAAR function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB). Here, the effects of acute blockade of neurosteroidogenesis by the 5α-reductase inhibitor finasteride on phasic and tonic GABAAR-mediated currents were examined in nRT and VB of mice. In nRT, finasteride altered the decay and amplitude, but not the frequency, of phasic currents, with no effect on tonic inhibition. In VB neurons, by contrast, finasteride reduced both the size and frequency of phasic currents, and also reduced the degree of tonic inhibition. These studies thus provide novel evidence for endogenous modulation of GABAAR function by 5α-reduced neurosteroids in the mature thalamus.",
keywords = "finasteride, GABA, neurosteroid, thalamus, tonic inhibition",
author = "Christian, {Catherine A.}",
year = "2019",
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language = "English (US)",
journal = "Synapse",
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AB - Neurosteroids are potent allosteric modulators of GABAA receptors (GABAARs). Although the effects of exogenous neurosteroids on GABAAR function are well documented, less is known about effects of neurosteroids produced by local endogenous biosynthesis. The neurosteroidogenic enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase are expressed in two nuclei of somatosensory thalamus, the thalamic reticular nucleus (nRT) and ventrobasal nucleus (VB). Here, the effects of acute blockade of neurosteroidogenesis by the 5α-reductase inhibitor finasteride on phasic and tonic GABAAR-mediated currents were examined in nRT and VB of mice. In nRT, finasteride altered the decay and amplitude, but not the frequency, of phasic currents, with no effect on tonic inhibition. In VB neurons, by contrast, finasteride reduced both the size and frequency of phasic currents, and also reduced the degree of tonic inhibition. These studies thus provide novel evidence for endogenous modulation of GABAAR function by 5α-reduced neurosteroids in the mature thalamus.

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