Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum
- Monash University, Australia
- Pennington Biomedical Research Center, United States
- Washington University in St. Louis, United States
- University of Newcastle, Australia
- University of Melbourne, Australia
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 hypothesized 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 minutes 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-6, Figure 1 - Figure Supplement 1&2, Figure 6 - Figure Supplement 1
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Author details
Funding
National Health and Medical Research Council (1126724)
- Zane B Andrews
National Health and Medical Research Council (1154974)
- Zane B Andrews
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were conducted in compliance with the Monash University Animal Ethics Committee guidelines (MARP 17855).
Copyright
© 2022, Reichenbach et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Metabolic sensing in AgRP neurons integrates homeostatic state with dopamine signalling in the striatum
eLife 11:e72668.
https://doi.org/10.7554/eLife.72668
