Glucose sensing by GABaergic neurons in the mouse nucleus tractus solitarii

Carie R. Boychuk, Peter Gyarmati, Hong Xu, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patchclamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose- inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCKdependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated.

Original languageEnglish (US)
Pages (from-to)999-1007
Number of pages9
JournalJournal of neurophysiology
Volume114
Issue number2
DOIs
StatePublished - Jun 18 2015
Externally publishedYes

Keywords

  • Brain stem
  • Glucokinase
  • Membrane potential
  • Vagus nerve

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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