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bioRxiv · 10.1101/2024.11.11.622987

Melanin concentrating hormone projections to the nucleus accumbens enhance the reward value of food consumption and do not induce feeding or REM sleep

Furman, K. L.·Baron, L.·Lyons, H. C.·Cha, T.·Evans, J. R.·Manna, J.·Zhu, L.·Mattis, J. H.·Burgess, C.
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Abstract

Regulation of food intake and energy balance is critical to survival. Hunger develops as a response to energy deficit and drives food-seeking and consumption. However, motivations to eat are varied in nature, and promoted by factors other than energy deficit. When dysregulated, non-homeostatic drives to consume can contribute to disorders of food intake, adding to the increasing prevalence of restrictive eating disorders and obesity. Melanin-concentrating hormone (MCH) neurons have been implicated in the regulation of feeding behavior, in addition to a number of other fundamental behaviors including sleep, anxiety, and maternal behavior. Several studies suggest that MCH peptide increases food consumption, while studies of MCH neurons show effects only on cued feeding, and others show no effect of MCH neuron manipulation on feeding. MCH neurons have widespread projections to diverse downstream brain regions yet few studies have investigated the function of specific projections or differentiated the behaviors they regulate. Here we use optogenetics, in combination with different behavioral paradigms, to elucidate the role of MCH projections to the nucleus accumbens (NAc) in sleep and feeding behavior. We show that MCH neurons projecting to the NAc do not induce changes in baseline feeding or REM sleep, but do enhance the preference for a food paired with optogenetic stimulation. Furthermore, this effect is diminished in female mice relative to males, in line with previous results suggesting sex differences in the functional role of MCH neurons. These results suggest that MCH projections to the NAc can enhance the rewarding value of consumed food. Significance StatementWhile feeding is often driven by hunger, there are non-homeostatic reasons why animals consume food. Melanin-concentrating hormone (MCH) neurons have been implicated in the regulation of many fundamental behaviors, including feeding, sleep and reward. They project broadly throughout the brain, suggesting that they may mediate this diverse set of behaviors independently via specific projections to downstream regions. We used optogenetic activation of MCH neurons and their projections to the nucleus accumbens (NAc) in combination with complex behavioral paradigms to demonstrate that MCH projections to the NAc do not induce baseline feeding or increases in REM sleep but do enhance the value of a paired food. These results suggest that MCH neurons contribute to non-homeostatic consumption via projections to the NAc.

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Furman, K. L., Baron, L., Lyons, H. C., Cha, T., Evans, J. R., Manna, J., Zhu, L., Mattis, J. H., Burgess, C.. 2024-11-12. Melanin concentrating hormone projections to the nucleus accumbens enhance the reward value of food consumption and do not induce feeding or REM sleep. https://doi.org/10.1101/2024.11.11.622987

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