Diabetes induces GABA receptor plasticity in murine vagal motor neurons

C. R. Boychuk, K. Cs Halmos, B. N. Smith

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Autonomic dysregulation accompanies type-1 diabetes, and synaptic regulation of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV) is altered after chronic hyperglycemia/hypoinsulinemia. Tonic gamma-aminobutyric acid A (GABAA) inhibition prominently regulates DMV neuron activity, which contributes to autonomic control of energy homeostasis. This study investigated persistent effects of chronic hyperglycemia/hypoinsulinemia on GABAA receptor-mediated inhibition in the DMV after streptozotocin-induced type-1 diabetes using electrophysiological recordings in vitro, quantitative (q)RT-PCR, and immunohistochemistry. Application of the nonspecific GABAA receptor agonist muscimol evoked an outward current of significantly larger amplitude in DMV neurons from diabetic mice than controls. Results from application of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP), a δ-subunit agonist, suggested that GABAA receptors containing δ-subunits contributed to the enhanced induc-ible tonic GABA current in diabetic mice. Sensitivity to THIP of inhibitory postsynaptic currents in DMV neurons from diabetic mice was also increased. Results from qRTPCR and immunohistochemical analyses indicated that the altered GABAergic inhibition may be related to increased trafficking of GABAA receptors that contain the δ-subunit, rather than an expression change. Overall these findings suggest increased sensitivity of δ-subunit containing GABAA receptors after several days of hyperglycemia/ hypoinsulinemia, which dramatically alters GABAergic inhibition of DMV neurons and could contribute to diabetic autonomic dysregulation.

Original languageEnglish (US)
Pages (from-to)698-706
Number of pages9
JournalJournal of neurophysiology
Volume114
Issue number1
DOIs
StatePublished - May 20 2015
Externally publishedYes

Keywords

  • Diabetes
  • GABA
  • Tonic current

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Fingerprint Dive into the research topics of 'Diabetes induces GABA receptor plasticity in murine vagal motor neurons'. Together they form a unique fingerprint.

  • Cite this