GABAergic Interneurons in the Insular Cortex Alleviate Acute Stress-Induced Gastric Injury by Suppressing the IC-NTS Glutamatergic Pathway.

Acute stress induces gastric mucosal injury, but the central mechanisms remain unclear. We investigated whether GABAergic interneurons, particularly somatostatin (SST) neurons, in the insular cortex (IC) are involved using restraint water-immersion stress (RWIS) in mice. RWIS upregulated GAD65 and SST but downregulated parvalbumin (PV) in the IC. Chemogenetic inhibition of IC GABAergic or SST neurons exacerbated gastric mucosal injury and reduced gastric tight junction proteins (Occludin, Claudins) and PCNA, whereas activation of SST neurons attenuated injury and increased these proteins. Inhibiting IC SST neurons projecting specifically to the nucleus tractus solitarius (NTS) did not affect injury. However, simultaneous inhibition of both SST and glutamatergic neurons in the IC significantly reduced injury and increased Occludin, Claudins, and PCNA levels compared to SST inhibition alone. Thus, IC SST neurons protect against RWIS-induced gastric injury by indirectly suppressing glutamatergic activity in the IC-NTS pathway.