Editors' ChoiceMetabolism

In the mood for food

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Science Translational Medicine  13 Sep 2017:
Vol. 9, Issue 407, eaao6124
DOI: 10.1126/scitranslmed.aao6124

Abstract

A neuronal subpopulation in the central amygdala promotes food consumption.

Food consumption is critical to human survival, and multiple neuropsychiatric disorders, including depression and anorexia nervosa, are associated with abnormal eating habits. Although prior work has established the role of central amygdala (CeA) in feeding and reward, elucidating the neuronal players and the mechanisms modulating food consumption may ultimately facilitate the discovery of novel pathophysiological pathways contributing to eating disorders. In this study, Douglas et al. discovered a subpopulation of serotonin 2A receptor-expressing neurons in the CeA (CeAHtr2a) that modulates positive reinforcement and food consumption in mice. Importantly, this cell population does not overlap with the protein kinase C-δ–expressing neurons (CeAPKCδ), which have previously been shown to suppress food consumption.

Using cell type–specific calcium imaging, the authors found that the activity of CeAHtr2a neurons signals eating. By directly stimulating these neurons using optogenetics or designer receptors exclusively activated by designed drugs (DREADDs), the authors also demonstrated that selective activation of CeAHtr2a neurons promoted food consumption both under normal conditions and under conditions of decreased motivation to eat. Ablating these cells or acutely suppressing their activity using optogenetics decreased food consumption under conditions where motivation to eat is normally high.

After establishing that CeAHtr2a neurons play a key role in regulating food consumption, the authors sought to determine the circuit mechanisms by which these cells modulate eating behaviors. Using synaptic tracing tools, they found that these inhibitory CeAHtr2a neurons directly innervate the parabrachial nucleus, a region implicated in appetite suppression, and local CeAPKCδ anorexinergic neurons. CeAHtr2a neurons also receive synaptic inputs from multiple other brain regions regulating reward-related behaviors and eating. Thus, CeAHtr2a neurons are hard-wired such that they can promote eating by inhibiting the activity of neurons that suppress food consumption upon reward- and food-related input signals.

Overall, the authors discovered a population of neurons in the CeA that, by integrating activity across multiple brain regions, regulates food consumption. Future studies aimed at probing the function of this subpopulation of neurons in health and disease may facilitate the development of novel therapeutics for treating altered eating behaviors across neuropsychiatric disorders.

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