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Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum
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Reichenbach, Alex, Clarke, Rachel E., Stark, Romana, Lockie, Sarah Haas, Mequinion, Mathieu, Dempsey, Harry, Rawlinson, Sasha, Reed, Felicia, Sepehrizadeh, Tara, DeVeer, Michael, Munder, Astrid C., Nunez-Iglesias, Juan, Spanswick, David C., Mynatt, Randall, Kravitz, Alexxai V., Dayas, Christopher V., Brown, Robyn and Andrews, Zane B. (2022) Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum. eLife, 11 . e72668. doi:10.7554/elife.72668 ISSN 2050-084X.
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Official URL: https://doi.org/10.7554/elife.72668
Abstract
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 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.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||
SWORD Depositor: | Library Publications Router | |||||||||
Library of Congress Subject Headings (LCSH): | Neuropeptides, Neurons, Metabolism, Dopamine | |||||||||
Journal or Publication Title: | eLife | |||||||||
Publisher: | eLife Sciences Publications Ltd. | |||||||||
ISSN: | 2050-084X | |||||||||
Official Date: | 12 January 2022 | |||||||||
Dates: |
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Volume: | 11 | |||||||||
Article Number: | e72668 | |||||||||
DOI: | 10.7554/elife.72668 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 23 February 2022 | |||||||||
Date of first compliant Open Access: | 24 February 2022 | |||||||||
RIOXX Funder/Project Grant: |
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