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Perinatal High Fat Diet Alters Development of GABAA Receptor Subunits in the Dorsal Motor Nucleus of the Vagus.

Perinatal high fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to A a subunits, while mRNA and protein expression were measured via qPCR and western blotting, respectively. pHFD decreased basal antrum and corpus motility, while brainstem microinjection of L838,417 (positive allosteric modulator of a2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA a1,2, and 3 subunits, however, did not differ between control and pHFD rats.. This study suggests that pHFD exposure arrests the development of synaptic GABAA a2/3 receptor subunits on DMV neurons, and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA a2/3 subunit-containing receptors implies such developmental changes may contribute to the observed decreased gastric motility.