GABAergic System in Stress: Implications of GABAergic Neuron Subpopulations and the Gut-Vagus-Brain Pathway

Abstract

Stress can cause a variety of central nervous system disorders, which are critically mediated by the γ-aminobutyric acid (GABA) system in various brain structures. GABAergic neurons have different subsets, some of which coexpress certain neuropeptides that can be found in the digestive system. Accumulating evidence demonstrates that the gut-brain axis, which is primarily regulated by the vagus nerve, is involved in stress, suggesting a communication between the "gut-vagus-brain" pathway and the GABAergic neuronal system. Here, we first summarize the evidence that the GABAergic system plays an essential role in stress responses. In addition, we review the effects of stress on different brain regions and GABAergic neuron subpopulations, including somatostatin, parvalbumin, ionotropic serotonin receptor 5-HT3a, cholecystokinin, neuropeptide Y, and vasoactive intestinal peptide, with regard to signaling events, behavioral changes, and pathobiology of neuropsychiatric diseases. Finally, we discuss the gut-brain bidirectional communications and the connection of the GABAergic system and the gut-vagus-brain pathway.

Figure 1

Potential role of crosstalk between the GABAergic system and the gut-vagus-brain pathway in stress. GABA, γ-aminobutyric acid; 5-HT3aR, serotonin receptor 5-HT3a; CCK, cholecystokinin; VIP, vasoactive intestinal peptide; SST, somatostatin; NPY, neuropeptide Y; PV, parvalbumin; mPFC, medial prefrontal cortex; PVH, paraventricular nucleus of the hypothalamus; NTS, nucleus of the solitary tract; DMN, dorsal motor nucleus; HPA, hypothalamic-pituitary-adrenal.