Metabolic rearrangement of fluorenone oxime to phenanthridinone

Summary Fluorenone oxime is metabolized in vivo in the rat to phenanthridinone which is excreted in the urine. The structure of the metabolite has been determined by comparison of chromatographic and spectral properties of the metabolites with authentic phenathridinone.Acknowledgments. This work was supported in part by NIH grant CA-18615 from the National Cancer Institute, DHEW.     

Deconstruction of a neural circuit for hunger

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.