The GABAb Receptor and Regulation of Gastric Motility

Special thanks to Dr. Stefano Vicini and Dr. Niaz Sahibzada from Georgetown University School of Medicine!

Abstract

GABAb RECEPTOR ACTIVITY IN SOMATOSTATIN POSITIVE INTERNEURONS INFLUENCE GASTRIC REGULATION AND FUNCTION

Elizabeth Kim, Georgetown University School of Medicine

Dr. Stefano Vicini, Georgetown University School of Medicine

Stomach tone and motility are carefully regulated through constant inhibitory input from GABAergic interneurons to the motor neurons of the dorsal motor nucleus of the vagus (DMV). Studies have found that somatostatin expressing interneurons (SST) provide a large component of the inhibitory GABAergic input to DMV motor neurons. Additionally, in vivo studies have shown that GABAb receptor activation through a GABAb receptor agonist (Baclofen) surprisingly stimulates DMV motor neurons and gastric motility, but the role of the GABAb receptor in this neural circuit is unknown. Using whole cell patch clamp and optogenetics with mice selectively expressing channelrhodopsin2 in SST-expressing interneurons, we examined the role of SST interneurons in the DMV on gastric motility in the presence of a GABAbR agonist. We observed overall decreased inhibitory signaling to both DMV motor neurons and SST interneurons with Baclofen perfusion, confirming previous findings that GABAbR stimulation in the DMV causes downstream gastric motility. GABAbR stimulation also induced an inhibitory outward current in postsynaptic DMV motor neurons and a reduction in the amplitude of light-evoked currents received by DMV motor neurons and SST interneurons from presynaptic SST interneurons. These findings suggest that the effect of GABAb receptor is predominantly on presynaptic SST cells at the SST-DMV synapse, whereby presynaptic GABAbR activation inhibits the GABA-producing SST interneurons, which allows DMV motor neuron firing, and finally stimulates gastric motility.

Technical Slides

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