AgRP neurons trigger long-term potentiation and facilitate food seeking

Authors: WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC); ZHOU, WENJUN - Baylor College Of Medicine; HE, YANG - Children'S Nutrition Research Center (CNRC); YANG, TIFFANY - Children'S Nutrition Research Center (CNRC); XU, PINGWEN - University Of Illinois; YANG, YONGJIE - Children'S Nutrition Research Center (CNRC); CAI, XING - Children'S Nutrition Research Center (CNRC); WANG, JULIA - Children'S Nutrition Research Center (CNRC); LIU, HESONG - Children'S Nutrition Research Center (CNRC); YU, MENG - Children'S Nutrition Research Center (CNRC); LIANG, CHEN - Children'S Nutrition Research Center (CNRC); YANG, TINGTING - Children'S Nutrition Research Center (CNRC); LIU, HAILAN - Children'S Nutrition Research Center (CNRC); FUKUDA, MAKOTO - Children'S Nutrition Research Center (CNRC); TONG, QINGCHUN - University Of Texas Health Science Center; WU, QI - Children'S Nutrition Research Center (CNRC); SUN, ZHENG - Baylor College Of Medicine; HE, YANLIN - Pennington Biomedical Research Center; XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Translational Psychiatry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2020
Publication Date: 1/5/2021
Citation: Wang, C., Zhou, W., He, Y., Yang, T., Xu, P., Yang, Y., Cai, X., Wang, J., Liu, H., Yu, M., Liang, C., Yang, T., Liu, H., Fukuda, M., Tong, Q., Wu, Q., Sun, Z., He, Y., Xu, Y. 2021. AgRP neurons trigger long-term potentiation and facilitate food seeking. Translational Psychiatry. 11. Article 11. https://doi.org/10.1038/s41398-020-01161-1.
DOI: https://doi.org/10.1038/s41398-020-01161-1

Interpretive Summary: Obesity, resulting overeating and energy imbalance, is serious health issue to our society but the mechanisms for the regulation of food seeking behavior is still elusive. Here we discovered a brain circuit that increases plasticity during food deprivation and facilitates food seeking behavior in mice. This work identified a potential target for obesity intervention.

Technical Abstract: Sufficient feeding is essential for animals' survival, which requires a cognitive capability to facilitate food seeking, but the neurobiological processes regulating food seeking are not fully understood. Here we show that stimulation of agouti-related peptide-expressing (AgRP) neurons triggers a long-term depression (LTD) of spontaneous excitatory post-synaptic current (sEPSC) in adjacent pro-opiomelanocortin (POMC) neurons and in most of their distant synaptic targets, including neurons in the paraventricular nucleus of the thalamus PVT). The AgRP-induced sEPCS LTD can be enhanced by fasting but blunted by satiety signals, e.g. leptin and insulin. Mice subjected to food-seeking tasks develop similar neural plasticity in AgRP-innervated PVT neurons. Further, ablation of the majority of AgRP neurons, or only a subset of AgRP neurons that project to the PVT, impairs animals' ability to associate spatial and contextual cues with food availability during food seeking. A similar impairment can be also induced by optogenetic inhibition of the AgRP->PVT projections. Together, these results indicate that the AgRP->PVT circuit is necessary for food seeking.