Two intermingled hypothalamic neuron populations specified by expression of agouti-related peptide (AGRP) or pro-opiomelanocortin (POMC) positively and negatively influence feeding behavior, respectively, possibly by reciprocally regulating downstream melanocortin receptors. However, the sufficiency of these neurons to control behavior and the relationship of their activity to the magnitude and dynamics of feeding are unknown. To measure this, we used channelrhodopsin-2 for cell type–specific photostimulation. Activation of only 800 AGRP neurons in mice evoked voracious feeding within minutes. The behavioral response increased with photoexcitable neuron number, photostimulation frequency and stimulus duration. Conversely, POMC neuron stimulation reduced food intake and body weight, which required melanocortin receptor signaling. However, AGRP neuron–mediated feeding was not dependent on suppressing this melanocortin pathway, indicating that AGRP neurons directly engage feeding circuits. Furthermore, feeding was evoked selectively over drinking without training or prior photostimulus exposure, which suggests that AGRP neurons serve a dedicated role coordinating this complex behavior.
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We thank G. Shtengel for assistance with photostimulation equipment and software, R. Shusterman for assistance with data analysis, H. Peng for image analysis tools, J. Osborne and T. Tabachnik for equipment design and fabrication, A. Arnold for imaging support, B. Shields and A. Hu for histology support, and J. Cox for mouse breeding and genotyping support. K. Svoboda, G. Murphy, J. Dudman, A. Lee, and S.E.R. Egnor commented on the manuscript. This research was funded by the Howard Hughes Medical Institute.
The authors declare no competing financial interests.
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Aponte, Y., Atasoy, D. & Sternson, S. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci 14, 351–355 (2011). https://doi.org/10.1038/nn.2739
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