{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:37:04Z","timestamp":1774946224042,"version":"3.50.1"},"reference-count":46,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R01DK056132"],"award-info":[{"award-number":["R01DK056132"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:p>Chronic experimentally induced hyperglycemia augments subunit-specific \u03b3-aminobutyric acid A (GABA<jats:sub>A<\/jats:sub>) receptor-mediated inhibition of parasympathetic preganglionic motor neurons in the dorsal motor nucleus of the vagus (DMV). However, the contribution of \u03b11 or \u03b3 GABA<jats:sub>A<\/jats:sub>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 \u03b11- and \u03b3-subunit-specific GABA<jats:sub>A<\/jats:sub>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 \u03b11-subunit-selective GABA<jats:sub>A<\/jats:sub>receptor-positive allosteric modulator zolpidem. Responses to low concentrations of the GABA<jats:sub>A<\/jats:sub>receptor antagonist gabazine suggested an additional increased contribution of \u03b3-subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in \u03b11- and \u03b3-subunit-dependent activity, transcription of both the \u03b11- and \u03b32-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.<\/jats:p><jats:p>NEW &amp; 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 GABA<jats:sub>A<\/jats:sub>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.<\/jats:p>","DOI":"10.1152\/jn.00085.2017","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T01:05:23Z","timestamp":1503536723000},"page":"2833-2841","source":"Crossref","is-referenced-by-count":13,"title":["Functional and molecular plasticity of \u03b3 and \u03b11 GABA<sub>A<\/sub>receptor subunits in the dorsal motor nucleus of the vagus after experimentally induced diabetes"],"prefix":"10.1152","volume":"118","author":[{"given":"Carie R.","family":"Boychuk","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katalin 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