@article{f0342c52652445d5931472d755153233,
title = "Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum",
abstract = "Agouti-related peptide (AgRP) neurons increase motivation for food, however, whether metabolic sensing of homeostatic state in AgRP neurons potentiates motivation by inter-acting 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 AgPP 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.",
author = "Alex Reichenbach and Clarke, {Rachel E.} and Romana Stark and Lockie, {Sarah Haas} and Mathieu Mequinion and Harry Dempsey and Sasha Rawlinson and Felicia Reed and Tara Sepehrizadeh and Michael Deveer and Munder, {Astrid C.} and Juan Nunez-Iglesias and Spanswick, {David C.} and Randall Mynatt and Kravitz, {Alexxai V.} and Dayas, {Christopher V.} and Robyn Brown and Andrews, {Zane B.}",
note = "Funding Information: We would like to thank Myles Billard from TDT for his valuable technical assistance and support with setting up photometry and analysis. We would like to thank Antonio (Nino) Benci at the Monash Instrumentation Facility for help with FED3 production and maintenance. The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at Monash Biomedical Imaging, Monash University. We would like to thank Professor Alex Fornito for the use of fDOPA in PET studies. We acknowledge that Bio Render was used to produce elements incorporated in the figure and graphical abstract (Biorender.com). Funding: National Health and Medical Research Council project grant APP1126724 (ZBA). National Health and Medical Research Council research fellowship APP1154974 (ZBA). Funding Information: We would like to thank Myles Billard from TDT for his valuable technical assistance and support with setting up photometry and analysis. We would like to thank Antonio (Nino) Benci at the Monash Instrumentation Facility for help with FED3 production and maintenance. The authors acknowledge the facilities and scientific and technical assistance of the National Imaging Facility, a National Collab-orative Research Infrastructure Strategy (NCRIS) capability, at Monash Biomedical Imaging, Monash University. We would like to thank Professor Alex Fornito for the use of fDOPA in PET studies. We acknowledge that Bio Render was used to produce elements incorporated in the figure and graph-ical abstract (Biorender.com). Funding: National Health and Medical Research Council project grant APP1126724 (ZBA). National Health and Medical Research Council research fellowship APP1154974 (ZBA). Publisher Copyright: {\textcopyright} 2022, eLife Sciences Publications Ltd. All rights reserved.",
year = "2022",
month = jan,
doi = "10.7554/eLife.72668",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
}