A hindbrain inhibitory microcircuit mediates vagally-coordinated glucose regulation

Scientific Reports
Carie R BoychukBret N Smith

Abstract

Neurons in the brainstem dorsal vagal complex integrate neural and humoral signals to coordinate autonomic output to viscera that regulate a variety of physiological functions, but how this circuitry regulates metabolism is murky. We tested the hypothesis that premotor, GABAergic neurons in the nucleus tractus solitarius (NTS) form a hindbrain micro-circuit with preganglionic parasympathetic motorneurons of the dorsal motor nucleus of the vagus (DMV) that is capable of modulating systemic blood glucose concentration. In vitro, neuronal activation or inhibition using either excitatory or inhibitory designer receptor exclusively activated by designer drugs (DREADDs) constructs expressed in GABAergic NTS neurons increased or decreased, respectively, action potential firing of GABAergic NTS neurons and downstream synaptic inhibition of the DMV. In vivo, DREADD-mediated activation of GABAergic NTS neurons increased systemic blood glucose concentration, whereas DREADD-mediated silencing of these neurons was without effect. The DREADD-induced hyperglycemia was abolished by blocking peripheral muscarinic receptors, consistent with the hypothesis that altered parasympathetic drive mediated the response. This effect was paralleled by ele...Continue Reading

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Citations

Sep 23, 2020·Pflügers Archiv : European journal of physiology·Jong-Woo Sohn, Won-Kyung Ho
Jun 5, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Erica L LittlejohnCarie R Boychuk
Oct 10, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jhansi Dyavanapalli
Oct 6, 2020·American Journal of Physiology. Endocrinology and Metabolism·Kyle D MedakDavid C Wright
Jul 30, 2020·Current Opinion in Pharmacology·Liliana Espinoza, Carie R Boychuk
Nov 19, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Soledad Pitra, Bret N Smith
Nov 27, 2020·Frontiers in Endocrinology·Jessica L HaighBeatrice M Filippi
Mar 19, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Courtney Clyburn, Kirsteen N Browning
Apr 20, 2021·Frontiers in Endocrinology·Alastair J MacDonaldKate L J Ellacott
Oct 31, 2021·Arthritis Research & Therapy·Takayuki MatsushitaFusao Kato
Jul 2, 2020·Physiology & Behavior·Linh LieuKevin W Williams

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Methods Mentioned

BETA
dissection
PCR
Protein Assay

Software Mentioned

pClamp
Mini
Graphpad Prism
MiniAnalysis
Clampfit
ImageJ
analysis

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