Projects per year
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.
Original language | English |
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Article number | e72668 |
Number of pages | 24 |
Journal | eLife |
Volume | 11 |
DOIs | |
Publication status | Published - Jan 2022 |
Projects
- 2 Finished
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Hunger-sensitive neural pathways influence appetite and behaviour
1/01/19 → 31/12/23
Project: Research
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Neural sensing of hunger links homeostatic and reward pathways
Andrews, Z., Luquet, S. & Horváth, T. L.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/17 → 31/12/19
Project: Research
Equipment
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Biomedical Imaging (MBI)
Kylie Reid (Manager), Robert Brkljaca (Manager), Christoph Hagemeyer (Other) & David Wright (Other)
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility