Functional and molecular plasticity of {gamma} and {alpha}1 GABAA receptor subunits in the dorsal motor nucleus of the vagus after experimentally induced diabetes

This study investigated the effect of chronic hyperglycemia/hypoinsulinemia on α1- and -subunit-specific GABAA 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 GABAA receptor-positive allosteric modulator zolpidem. Responses to low concentrations of the GABAA receptor antagonist gabazine suggested an additional increased contribution of -subunit-containing receptors to tonic currents in DMV neurons. Consistent with the functional elevation in α1- and -subunit-dependent activity, transcription of both the α1- and 2-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 ...
Source: Journal of Neurophysiology - Category: Neurology Authors: Tags: Research Articles Source Type: research