Deconstruction of a neural circuit for hunger

By Deniz Atasoy, J. N. Betley, H. Su, Scott Sternson. Nature, 2012

889 citations recorded by the source corpus.

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.

View Paper: https://www.semanticscholar.org/paper/c43b2a0bbe3edcefb5018e05336790914f6aba4a

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Citations in the corpus

• Neuropeptide transmission in brain circuits (2012, background): “Both NPY and GABA inhibition of paraventricular oxytocin cells contributed to the initiation of feeding (Atasoy et al, 2012); the role of the GABA projection from the AgRP/NPY neuron to the PBN was interpreted in the context of visceral malaise.”
• Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males (2013, unknown): “L) and controls feeding and the estrous cycle (Atasoy et al., 2012; Simerly, 2002).”
• DREADDs for Neuroscientists (2016, methodology): “…then, hM3Dq has been widely used to enhance neuronal firing, and I here cite only representative examples in which feeding (Krashes et al., 2011; Atasoy et al., 2012), energy expenditure (Kong et al., 2012), locomotion and striatal synaptogenesis (Kozorovitskiy et al., 2012), memory (Garner et…”
• A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior (2015, unknown): “PVHSIM1 neurons (Figs 3A and 3B), which make up the vast majority of PVH cells, have been previously demonstrated to increase food intake when chemogenetically inhibited (Atasoy et al., 2012; Stachniak et al., 2014).”
• The Oxytocin Receptor: From Intracellular Signaling to Behavior. (2018, background): “Similarly, direct optogenetic activation of PVN OXT neurons resulted in suppressed food intake (42).”
• Physiology of Astroglia. (2018, unknown): “Food intake is controlled by two populations of hypothalamic neurons: agouti-related protein (AGRP) expressing neurons that stimulate food intake and pro-opiomelanocortin (POMC) neurons that inhibit food-seeking behavior (73).”