Vagal GABAergic signaling in autonomic control of cardiometabolic function

Gamma-aminobutyric acid (GABA) and its receptors play a critical role in maintaining the balance between excitatory and inhibitory neurotransmission in the central nervous system, including autonomic regulatory regions that control cardiometabolic function. The vagal circuits facilitate bidirectional communication between peripheral organs and the brain to elicit autonomic reflexes and modulate complex adaptive behavior to preserve cardiometabolic homeostasis. Dampened vagal activity can lead to the development of cardiometabolic diseases. Emerging evidence over the past decade identifies inhibitory GABAergic signaling in key vagal regulatory regions as a potential mechanism underlying vagal dysfunction linked to cardiometabolic disease. In this review, we discuss recent studies exploring GABAergic signaling modulation in vagal circuits, focusing on the regulation of food intake, cardiac function, and glucose metabolism-critical physiological processes that are often disrupted in cardiometabolic disease. We outline GABAergic signaling properties within key vagal reflex circuits, namely, vagal sensory afferents, nucleus tractus solitarius, and vagal motor neurons, and discuss how cardiometabolic stressors, as well as disease states, remodel vagal GABAergic signaling.