Functional and molecular plasticity of γ and α1 GABA a receptor subunits in the dorsal motor nucleus of the vagus after experimentally induced diabetes

Carie R. Boychuk, Katalin C. Smith, Bret N. Smith

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Chronic experimentally induced hyperglycemia augments subunit-specific γ-aminobutyric acid A (GABAA) receptor-mediated inhibition of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). However, the contribution of α1 or γ GABA A receptor subunits, which are ubiquitously expressed on central nervous system neurons, to this elevation in inhibitory tone have not been determined. This study investigated the effect of chronic hyperglycemia/hypoinsulinemia on α1- and γ-subunit-specific GABA A receptor-mediated inhibition using electrophysiological recordings in vitro and quantitative RT-PCR. DMV neurons from streptozotocin-treated mice demonstrated enhancement of both phasic and tonic inhibitory currents in response to application of the α1-subunit-selective GABA A receptor-positive allosteric modulator zolpidem. Responses to low concentrations of the GABA A receptor antagonist gabazine suggested an additional increased contribution of γ-subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in α1- and γ-subunit-dependent activity, transcription of both the α1- and γ2-subunits was increased in the dorsal vagal complex of streptozotocin- treated mice. Overall, these findings suggest an increased sensitivity to both zolpidem and gabazine after several days of hyperglycemia/hypoinsulinemia, which could contribute to altered parasympathetic output from DMV neurons in diabetes. NEW & NOTEWORTHY Glutamate and GABA signaling in the dorsal vagal complex is elevated after several days of chronic hyperglycemia in a mouse model of type 1 diabetes. We report persistently enhanced GABAA receptor-mediated responses to the somnolescent zolpidem in preganglionic vagal motor neurons. These results imply a broader impact of chronic hyperglycemia on central vagal function than previously appreciated and reinforce the hypothesis that diabetes effects in the brain can impact regulation of metabolic homeostasis.

Original languageEnglish (US)
Pages (from-to)2833-2841
Number of pages9
JournalJournal of neurophysiology
Volume118
Issue number5
DOIs
StatePublished - Nov 9 2017

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Keywords

  • GABA
  • Hyperglycemia
  • Patch clamp
  • Vagus
  • Zolpidem

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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