AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training

Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia, USA.
Nature Neuroscience (Impact Factor: 14.98). 03/2011; 14(3):351-5. DOI: 10.1038/nn.2739
Source: PubMed

ABSTRACT 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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Available from: Scott M Sternson, Aug 06, 2015
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    • "negatively regulate feeding behaviors (Aponte et al., 2011). "
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    • "Studies in previous decades have revealed apparently opposite functions for POMC neurons and AgRP neurons in regulating food intake. Stimulating POMC neurons in the ARC and NTS suppresses feeding (Aponte et al., 2011; Zhan et al., 2013), whereas stimulating AgRP neurons rapidly elicits feeding behavior (Aponte et al., 2011; Krashes et al., 2011). By contrast, killing POMC neurons induces hyperphagia and obesity (Yaswen et al., 1999; Coll et al., 2004; Xu et al., 2005; Zhan et al., 2013), whereas ablating AgRP neurons in adult mice induces hypophagia and, ultimately, starvation (Gropp et al., 2005; Luquet et al., 2005). "
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    • "Several studies have used opto-and chemogenetic techniques to attempt to manipulate the activity of varying genetically targeted populations of neurons with a role in feeding behavior and metabolism, including but not limited to AgRP neurons (Aponte et al., 2011; Atasoy et al., 2012; Krashes et al., 2011; Krashes et al., 2013) and Pomc neurons (Aponte et al., 2010; Zhan et al., 2013). Stimulation of arcuate Pomc neurons resulted in a reduction in food intake, whereas activation of arcuate AgRP neurons resulted in increased food intake and food-seeking behaviors (Aponte et al., 2010; Krashes et al., 2011; Zhan et al., 2013). The Pomc-induced reduction in food intake was dependent upon melanocortin receptors within the paraventricular hypothalamus (PVH), a hypothalamic nucleus that is a direct target of arcuate melanocortin neurons. "
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