期刊
TRANSLATIONAL PSYCHIATRY
卷 11, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41398-020-01161-1
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资金
- NIH [R01 DK114279, R01DK109934, R21NS108091, R00DK107008, R01ES027544, K01DK119471, 1R01DK109194, 1R56DK109194, P01DK113954, R01DK115761, R01DK117281, R01DK120858, P30HD024064]
- Pew Charitable Trust awards [0026188]
- Baylor Collaborative Faculty Research Investment Program grants
- USDA/CRIS [51000-064-01S]
- American Diabetes Association [7-13-JF-61, 1-17-PDF-138, 1-19-PDF-012, 1-15-BS-184]
- American Heart Association [16POST27260254, 20POST35120600]
Sufficient feeding is essential for animals' survival, and the neurobiological processes regulating food seeking behavior have been partially understood, in which the AgRP -> PVT circuit is crucial for food seeking.
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.
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