High‐Fat Diet Induced Modulation of Glutamatergic Currents in Neurons of the Dorsal Motor Nucleus of the Vagus Increases Gastric Tone and Motility

Abstract

Understanding how vagally‐mediated neurocircuits are affected by alterations in diet is crucial to addressing dysregulated feeding behaviors and energy balance, as well as their role in the development of obesity. We have demonstrated previously that acute high fat diet (HFD) exposure modulates glutamatergic neurotransmission to vagal efferent motoneurons. The purpose of this study was to test the hypothesis that acute HFD increases activation of synaptic NMDA receptors (NMDA‐R) on gastric‐projecting dorsal motor nucleus of the vagus (DMV) neurons, which increases vagal efferent drive to the stomach.Sprague Dawley rats (4–8 weeks of age) of both sexes were fed a control diet (14% kcal from fat) throughout the study, or a HFD (60% kcal from fat) for 3–5 days prior to experimentation. Daily food intake was measured from singly‐housed rats for 4 days prior and throughout exposure to HFD. Whole cell patch clamp recordings of gastric‐projecting DMV neurons were made from thin (300μm) brainstem slices. The effects of the NMDA‐R antagonist, AP5 (25μM) on amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) as well as action potential firing (AP) firing rate were examined. In vivo recordings of gastric motility and tone were made in response to microinjection of the non‐selective ionotropic glutamate antagonist, kynurenic acid (100pmol/60nL) and AP5 (500pmol/60nL).HFD exposure had no significant effect on caloric intake (control 55±4kcal/24hr vs acute HFD 59±9kcal/24hr; p>0.05) during the acute (3–5 day) period of study. After acute exposure to HFD, however, 9/15 DMV neurons responded to AP5 with a significant decrease in mEPSC amplitude and frequency (24.6±2.9pA vs 17.5±1.7pA; 1.4±0.3 pulses per second (p.p.s) vs 0.5±0.1p.p.s, respectively P<0.05 for each) as compared to only 1/18 control neurons. (18.7±1.3pA vs 18.0±1.3pA, P>0.05). In control conditions, AP5 had no effect on AP firing rate on 7/10 neurons (40.0±4.8 events/30sec vs 47.9±6.5 events/30sec, P>0.05), however, firing rate was decreased significantly in 5/5 neurons following acute HFD exposure (27.4±4.87 events/30sec vs 21.1±13.6 events/30sec, P<0.05). Brainstem microinjection of kynurenic acid had no effect on antral motility in control rats (102.5±17.6% of baseline, P>0.05), but significantly reduced motility following acute HFD exposure (59.9±1.10% of baseline, P<0.05).These data suggest that acute HFD exposure increases NMDA‐R activation, increases DMV neuronal excitability and, subsequently, vagal efferent control of gastric motility. Since this NMDA‐R activation is observed only during periods of caloric balance, these results suggest that plasticity within vagal neurocircuit glutamatergic signaling may be a critical homeostatic response to altered diet that helps maintain appropriate feeding behavior and caloric intake to defend against the development of obesity.Support or Funding InformationNSF IOS1148079 to Kirsteen BrowningThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.