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

By Yexica Aponte, Deniz Atasoy, Scott Sternson. Nature Neuroscience, 2010

1,067 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/314f9bf158e96c406c868b6a40cd3cb98bec14ec

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

1. Bryan L. Roth
2. G. Dienel
3. M. Krashes
4. Bradford B. Lowell

In Endocrine and Autonomic Systems

1. Bryan L. Roth
2. M. Krashes
3. Bradford B. Lowell
4. Haiming Cao
5. G. Hotamışlıgil

Citations in the corpus

• A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior (2015, positive): “…experiment to work, extensive restraint of ARCAgRP neuron activity is necessary to overcome the chemogenetically-induced feeding response given that only ~10% of ARCAgRP neurons are required to drive the full magnitude of food intake (Aponte et al., 2011; Betley et al., 2013; Krashes et al., 2013).”
• A Molecular Census of Arcuate Hypothalamus and Median Eminence Cell Types (2017, methodology): “For instance, orexigenic AgRP neurons and anorexigenic POMC neurons control feeding 3, 4 , while KISS1 neurons regulate serum luteinizing hormone levels 5 .”
• Sugar for the brain: the role of glucose in physiological and pathological brain function (2013, background): “supply to the brain [49, 51], peripheral nutrient uptake [49, 51] and utilization [67], as well as feeding [67-69].”
• DREADDs for Neuroscientists (2016, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 2 Examples for Apparent Equivalency of Chemo- and Optogenetic Modulation Cell Type DREADD Opsin Electrophysiology Behavior AgRP Neurons hM3Dq (Krashes et al., 2011) ChR2 (Aponte et al., 2011) Increased firing Enhan”