Deconstruction of a neural circuit for hunger.
Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.
Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive Ashburn, Virginia 20147, USA.
Deniz
D
Atasoy
J Nicholas
JN
Betley
Helen H
HH
Su
Scott M
SM
Sternson
D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005508:Food Deprivation; D006815:Hunger / Q000502:physiology*; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D013217:Starvation; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D011333:Pro-Opiomelanocortin