TY - JOUR TI - Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum AU - Reichenbach, Alex AU - Clarke, Rachel E AU - Stark, Romana AU - Lockie, Sarah Haas AU - Mequinion, Mathieu AU - Dempsey, Harry AU - Rawlinson, Sasha AU - Reed, Felicia AU - Sepehrizadeh, Tara AU - DeVeer, Michael AU - Munder, Astrid C AU - Nunez-Iglesias, Juan AU - Spanswick, David C AU - Mynatt, Randall AU - Kravitz, Alexxai V AU - Dayas, Christopher V AU - Brown, Robyn AU - Andrews, Zane B A2 - Palmiter, Richard D A2 - Westbrook, Gary L A2 - Palmiter, Richard D A2 - Herzog, Herbert VL - 11 PY - 2022 DA - 2022/01/12 SP - e72668 C1 - eLife 2022;11:e72668 DO - 10.7554/eLife.72668 UR - https://doi.org/10.7554/eLife.72668 AB - Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by interacting with dopamine reward systems is unexplored. As a model of impaired metabolic-sensing, we used the AgRP-specific deletion of carnitine acetyltransferase (Crat) in mice. We hypothesised that metabolic sensing in AgRP neurons is required to increase motivation for food reward by modulating accumbal or striatal dopamine release. Studies confirmed that Crat deletion in AgRP neurons (KO) impaired ex vivo glucose-sensing, as well as in vivo responses to peripheral glucose injection or repeated palatable food presentation and consumption. Impaired metabolic-sensing in AgRP neurons reduced acute dopamine release (seconds) to palatable food consumption and during operant responding, as assessed by GRAB-DA photometry in the nucleus accumbens, but not the dorsal striatum. Impaired metabolic-sensing in AgRP neurons suppressed radiolabelled 18F-fDOPA accumulation after ~30 min in the dorsal striatum but not the nucleus accumbens. Impaired metabolic sensing in AgRP neurons suppressed motivated operant responding for sucrose rewards during fasting. Thus, metabolic-sensing in AgRP neurons is required for the appropriate temporal integration and transmission of homeostatic hunger-sensing to dopamine signalling in the striatum. KW - AgRP KW - photometry KW - FED3 KW - motivation KW - fasting KW - dopamine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -