Identification of a Brainstem Circuit Controlling Feeding

Publication date: 27 July 2017
Source:Cell, Volume 170, Issue 3
Author(s): Alexander R. Nectow, Marc Schneeberger, Hongxing Zhang, Bianca C. Field, Nicolas Renier, Estefania Azevedo, Bindiben Patel, Yupu Liang, Siddhartha Mitra, Marc Tessier-Lavigne, Ming-Hu Han, Jeffrey M. Friedman
Hunger, driven by negative energy balance, elicits the search for and consumption of food. While this response is in part mediated by neurons in the hypothalamus, the role of specific cell types in other brain regions is less well defined. Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular transporters for GABA or glutamate (hereafter, DRN^Vgat and DRN^VGLUT3 neurons), are reciprocally activated by changes in energy balance and that modulating their activity has opposite effects on feeding—DRN^Vgat neurons increase, whereas DRN^VGLUT3 neurons suppress, food intake. Furthermore, modulation of these neurons in obese (ob/ob) mice suppresses food intake and body weight and normalizes locomotor activity. Finally, using molecular profiling, we identify druggable targets in these neurons and show that local infusion of agonists for specific receptors on these neurons has potent effects on feeding. These data establish the DRN as an important node controlling energy balance.PaperClip

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Teaser

A combination of brain mapping and molecular pharmacology approaches identifies specific neurons in the dorsal raphe nucleus as being important regulators of feeding behavior.


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