Maternal High Fat Diet Induces the Expression of an Inhibitory Glycinergic Current in Rat Dorsal Motor Nucleus of the Vagus Neurons Regulating Gastric Functions

Abstract

The perinatal period is critically important in the development of autonomic neurocircuits and maternal overnutrition during this period has been shown to predispose offspring to obesity and associated comorbidities. Previous studies suggest there is an increased inhibition of gastric projecting dorsal motor nucleus of the vagus nerve (DMV) neurons in rats fed a high fat diet (HFD) during the perinatal period, but the underlying neural mechanisms and the effects on gastric motility have yet to be determined. This aim of this study was to assess the effects of perinatal HFD on (i) inhibitory synaptic inputs to gastric‐projecting DMV neurons and (ii) gastric tone and motility.Whole cell patch clamp recordings were made from gastric projecting DMV neurons in thin brainstem slices from Sprague‐Dawley rats (4–6 weeks of age) fed either a control or HFD (14 or 60%kcal from fat, respectively) from embryonic day 13. Gastric motility and tone was measured via miniature strain gauges attached to the antrum of anesthetized rats.In the present study, perinatal HFD rats were not significantly heavier than age‐matched control rats (6 weeks; 232±17g vs 209±5g). The glycine receptor antagonist, strychnine (1μM), induced a larger inward current in perinatal HFD vs control DMV neurons (23±2pA vs 3±1pA, n=8, P<0.05), suggesting that glycine is a tonically released neurotransmitter in perinatal HFD, but not control, rats. Strychnine also increased the rise time (5.0±0.3ms vs 3.5±0.2ms), decay time (9.5±0.8ms vs 5.3±0.6ms), and half width (8.8±0.9ms vs 5.0±0.5ms) of miniature inhibitory postsynaptic currents (mIPSCs) in perinatal HFD (n=5, P<0.05 vs baseline for each parameter) but had no effect in control neurons rise time (3.45±0.2ms vs 3.7±0.2ms), decay time (4.5±0.3ms vs 4.9±0.5ms), or half‐width (4.3±0.3ms vs 4.8±0.5ms) of miniature postsynaptic currents (n=5, P>0.05 for each). Microinjection of strychnine (300pmoles/60nl) into the DMV increased gastric tone and motility in the antrum in perinatal HFD rats (82–101mg, 20–25% of baseline, respectively, n=2) but not in control rats (11–21mg, 2–10% of baseline, n=2, P<0.05 vs perinatal HFD for each), suggesting the tonic glycinergic inputs onto DMV neurons decreased vagal efferent outflow and reduced basal gastric motility and tone.The studies suggest that perinatal overnutrition induces the expression of a novel tonic glycinergic input onto gastric projecting DMV neurons, increasing the inhibitory drive to the stomach. Such alterations in brainstem neurocircuit development as a consequence of maternal over‐nutrition may induce gastric dysmotility and dysregulated gastointestinal reflexes, hence influencing offspring to develop obesity.Support or Funding InformationFunded by NIH 078364 and NSF IOS1148978