Sex Differences in GABAergic Neurotransmission to Gastric‐Projecting DMV Neurons

Abstract

Women have a higher prevalence of functional gastrointestinal (GI) disorders compared to men. Gastric motility is modulated by neurons of the dorsal motor nucleus of the vagus (DMV) and the activity of these neurons is regulated by a tonic GABAergic input. In general, females have been shown to have a higher expression of GABA throughout the central nervous system. The aim of this study was to investigate sex differences in the basic properties and GABAergic inputs to gastric-projecting DMV neurons. In an in vivo anesthetized preparation, microinjections of bicuculline methiodide (BIC, 0.5-50pmoles/60 nl) into the DMV of Sprague-Dawley rats increased gastric tone in a dose-dependent manner. Microinjection of 0.5 pmoles of BIC elicited a 32.0±12 mg increase in gastric tone (N=2) in males and a significantly greater increase in gastric tone in females (200.5±37; N=3; p<0.05). Whole-cell patch-clamp recordings were made from gastric-projecting DMV neurons. Female rats displayed an increased afterhyperpolarization amplitude (19.8±1 mV, N=18) compared to males (15.3±1 mV N=18; p<0.05), and a lower action potential frequency response to injection of 280 pA of current (31.5±2 events/s in males; 25.5±2 events/s in females). Perfusion of slices with BIC (0.5-50 μM) increased the firing rate of gastric-projecting neurons. The increase in the firing rate during perfusion with 50 μM BIC was significantly greater in females (237±53% of baseline; n=5) than in males (136.2±24%, n=3; p<0.05). These data show that gastric-projecting DMV neurons in females are less excitable and receive a higher tonic GABAergic input compared to males and suggest that reduced gastric motility in females may be due to a an increased inhibitory input to gastric-projecting neurons. Supported by: NIH DK55330