Qianru Zhao, Bing Feng, Vicky Dong, Lee How Lau, Hailan Liu, Meng Yu, Keqin Liang, Cindy Tran, Heidi Feng, Taylor Smiley, Peiyu Gao, Amy Yan, Hui Ye, Yuwei Jiang, Chunmei Wang, Pingwen Xu, Yanlin He
During pregnancy, physiological changes can alter food intake behaviors. However, the underlying neural mechanisms remain unclear. Here we show that female mice exhibit food-craving-like behavior during pregnancy, mirroring many patterns described in humans. We show that 5-HTDRN neuronal firing activity is reduced during pregnancy through increased small-conductance calcium-activated potassium type 3 (SK3) ion-channel activity. Genetic knockout of SK3 ion channels from 5-HTDRN neurons abolishes the pregnancy-associated suppression in 5-HTDRN neuronal firing activity and reduces food-craving-like behavior in pregnant mice. Conversely, overexpression of SK3 in 5-HTDRN neurons mimics pregnancy-induced food-craving-like behavior in virgin female mice. Moreover, activation of 5-HTDRN projections to ventral tegmental area inhibits food-craving-like behavior in pregnant mice. These findings provide novel insights into the role of 5-HT signaling in modulating food cravings during pregnancy and highlight potential targets for managing pregnancy-associated appetite dysregulation and maternal obesity in humans.