New insight into GABAergic neurons in the hypothalamic feeding regulation

Abstract

Several lines of study have suggested that GABA in the hypothalamic feeding center plays a role in promoting food intake. Recent studies revealed that not only NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) that co-express GABA but also other GABAergic neurons act as an orexigenic. Here, we review the progress of studies on hypothalamic GABAergic neurons distributed in ARC, dorsomedial hypothalamus (DMH), and lateral hypothalamus (LH). Three advanced technologies have been applied and greatly contributed to the recent progress. Optogenetic (and chemogenetic) approaches map input and output pathways of particular subpopulations of GABAergic neurons. In vivo Ca²⁺ imaging using GRIN lens and GCaMP can correlate the activity of GABAergic neuron subpopulations with feeding behavior. Single-cell RNA-seq approach clarifies precise transcriptional profiles of GABAergic neuron subpopulations. These approaches have shown diversity of GABAergic neurons and the subpopulation-dependent role in feeding regulation.

Keywords: Food intake; GABAergic neurons; Hypothalamus; NPY/AgRP neruons.

Fig. 1

Schematic overview of circuit of GABAergic neurons in hypothalamus in feeding regulation. Orange indicates GABAergic and blue indicates glutamatergic neurons. The dotted lines indicate nuclei. ARC arcuate nucleus, PVN paraventricular nucleus of hypothalamus, DMH dorsomedial hypothalamus, VMH ventromedial hypothalamus, LH lateral hypothalamus, CeA central nucleus of amygdala, aBNST anterior bed nucleus of the stria terminalis, PVT paraventricular nucleus of thalamus, PAG periaqueductal gray, PBN parabrachial nucleus, NPY neuropeptide Y, AgRP agouti-related protein, POMC proopiomelanocortin, Pdx-1 pancreas–duodenum homeobox 1, RIP rat insulin promoter1, MC4R melanocortin receptor 4, PACAP pituitary adenylate cyclase-activating polypeptide, TRH thyrotropin-releasing hormone, CRH corticotropin-releasing hormone, Oxt oxytocin, LepR leptin receptor, MCH melanin-concentrating hormone (color figure online)