The underlying neural network of proopiomelanocortin (POMC)-mediated regulation in food intake

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIDDK	NEURO-16

* FARE Award Winner

Authors

• C Li
• MJ Krashes

Abstract

Recent studies have demonstrated the functional roles of proopiomelanocortin (POMC) and agouti-related peptide (AGRP) neurons in the arcuate nucleus (ARC) of the hypothalamus. Respectively, they have been shown to promote and attenuate weight-gain and feeding behavior. Although much attention has focused on AGRPARC functions and projections, the axonal targets and mechanisms underlying POMCARC stimulation-induced satiety are unknown. POMCARC neurons release alpha-melanocyte-releasing hormone (α-MSH), a melanocortin-4 receptor (MC4R) agonist, which acts to reduce food intake. In contrast, AGRP neurons release the neuropeptides AGRP, an MC4R inverse agonist/antagonist, neuropeptide Y (NPY) and the neurotransmitter GABA, all of which drive feeding. These results suggest a highly orchestrated modulatory balance on appetite-controlling MC4R-expressing neurons. It has also been shown that the drop in body weight and food intake following 24-hr optogenetic activation of POMCARC soma is dependent on melanocortin signaling, suggesting MC4R-expressing neurons as likely targets for POMCARC neurons in mediating feeding. In this study, we determined the anatomical and cellular downstream targets of the POMCARC neurons mediating satiety with a focus on those expressing MC4R. In addition, we investigated the functional connection between POMCARC and MC4R-expressing neurons, as well as measure firing activity in these downstream neurons in distinct physiological hunger states.

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