D1 and D2 neurons in the nucleus accumbens enable positive and negative control over sugar intake in mice

Abstract

Although the consumption of carbohydrates is needed for survival, their potent reinforcing properties drive obesity worldwide. In turn, sugar overconsumption reveals a major role for brain reward systems in regulating sugar intake. However, it remains elusive how different cell types within the reward circuitries control the initiation and termination of sugary meals. Here, we identified the distinct nucleus accumbens cell types that mediate the chemosensory versus postprandial properties of sweet sugars. Specifically, D1 neurons enhance sugar intake via specialized connections to taste ganglia, whereas D2 neurons mediate the termination of sugary meals via anatomical connections to circuits involved in appetite suppression. Consistently, D2, but not D1, neurons partially mediate the satiating effects of glucagon-like peptide 1 (GLP-1) agonists. Thus, these nucleus accumbens cell types function as a behavioral switch, enabling positive versus negative control over sugar intake. Our study contributes to unveiling the cellular and circuit substrates of sugar overconsumption.