PT - JOURNAL ARTICLE AU - Yuhan Pu AU - Melissa Megan Masserant Palombo AU - Yiwen Zhang AU - Ping Shen TI - Gated Coupling of Dopamine and Neuropeptide Signaling Underlies Perceptual Processing of Appetitive Odors in <em>Drosophila</em> AID - 10.1101/159897 DP - 2017 Jan 01 TA - bioRxiv PG - 159897 4099 - http://biorxiv.org/content/early/2017/07/05/159897.short 4100 - http://biorxiv.org/content/early/2017/07/05/159897.full AB - How olfactory stimuli are perceived as meaningful cues for specific appetitive drives remains poorly understood. Here we show that despite their enormous diversity, Drosophila larvae can discriminatively respond to food-related odor stimuli based on both qualitative and quantitative properties. Perceptual processing of food scents takes place in a neural circuit comprising four dopamine (DA) neurons and a neuropeptide F (NPF) neuron per brain hemisphere. Furthermore, these DA neurons integrate and compress inputs from second-order olfactory neurons into one-dimensional DA signals, while the downstream NPF neuron assigns appetitive significance to limited DA outputs via a D1-type DA receptor (DoplR1)-mediated gating mechanism. Finally, Dop1R, along with a Gβ13F/Irk2-mediated inhibitory and a Gαs-mediated excitatory pathway, underlie a binary precision tuning apparatus that restricts the excitatory response of NPF neurons to DA inputs that fall within an optimum range. Our findings provide fresh molecular and cellular insights into cognitive processing of olfactory cues.