AgRP Neurons Trigger Long-Term Potentiation and Facilitate Food Seeking

Authors

Chunmei Wang
Wenjun Zhou
Yang He
Tiffany Yang
Pingwen Xu
Yongjie Yang
Xing Cai
Julia Wang
Hesong Liu
Meng Yu
Chen Liang
Tingting Yang
Hailan Liu
Makoto Fukuda
Qingchun Tong
Qi Wu
Zheng Sun
Yanlin He
Yong Xu

Publication Date

1-5-2021

Journal

Translational Psychiatry

DOI

10.1038/s41398-020-01161-1

PMID

33414382

PMCID

PMC7791100

PubMedCentral® Posted Date

1-5-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Agouti-Related Protein, Animals, Long-Term Potentiation, Mice, Neurons, Paraventricular Hypothalamic Nucleus, Pro-Opiomelanocortin, Learning and memory, Physiology

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.