Institute for Neuroscience, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology, ETH Zurich, 8603, Schwerzenbach, Switzerland.
Mol Psychiatry. 2023 Aug;28(8):3531-3547. doi: 10.1038/s41380-023-02131-x. Epub 2023 Jul 4.
Overeating is driven by both the hedonic component ('liking') of food, and the motivation ('wanting') to eat it. The nucleus accumbens (NAc) is a key brain center implicated in these processes, but how distinct NAc cell populations encode 'liking' and 'wanting' to shape overconsumption remains unclear. Here, we probed the roles of NAc D1 and D2 cells in these processes using cell-specific recording and optogenetic manipulation in diverse behavioral paradigms that disentangle reward traits of 'liking' and 'wanting' related to food choice and overeating in healthy mice. Medial NAc shell D2 cells encoded experience-dependent development of 'liking', while D1 cells encoded innate 'liking' during the first food taste. Optogenetic control confirmed causal links of D1 and D2 cells to these aspects of 'liking'. In relation to 'wanting', D1 and D2 cells encoded and promoted distinct aspects of food approach: D1 cells interpreted food cues while D2 cells also sustained food-visit-length that facilitates consumption. Finally, at the level of food choice, D1, but not D2, cell activity was sufficient to switch food preference, programming subsequent long-lasting overconsumption. By revealing complementary roles of D1 and D2 cells in consumption, these findings assign neural bases to 'liking' and 'wanting' in a unifying framework of D1 and D2 cell activity.
过量进食是由食物的享乐成分(“喜欢”)和进食的动机(“想要”)驱动的。伏隔核(NAc)是一个关键的大脑中枢,参与这些过程,但 NAc 细胞群体如何分别编码“喜欢”和“想要”以形成过度消费仍然不清楚。在这里,我们使用细胞特异性记录和光遗传学操纵,在不同的行为范式中探究了 NAc D1 和 D2 细胞在这些过程中的作用,这些范式分离了与健康小鼠的食物选择和过度进食相关的“喜欢”和“想要”的奖励特征。内侧 NAc 壳 D2 细胞编码了经验依赖性的“喜欢”发展,而 D1 细胞在第一次品尝食物时编码了先天的“喜欢”。光遗传学控制证实了 D1 和 D2 细胞与“喜欢”这些方面的因果关系。在与“想要”相关的方面,D1 和 D2 细胞编码并促进了食物接近的不同方面:D1 细胞解释食物线索,而 D2 细胞也维持了促进消费的食物访问长度。最后,在食物选择的水平上,D1 细胞而不是 D2 细胞的活动足以改变食物偏好,从而编程随后的长期过度消费。通过揭示 D1 和 D2 细胞在消费中的互补作用,这些发现将“喜欢”和“想要”分配到 D1 和 D2 细胞活动的统一框架中的神经基础。