Arnold Rachel A, Peterson BreeAnne, Peters James Henry
Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States.
Am J Physiol Cell Physiol. 2025 Sep 1;329(3):C812-C820. doi: 10.1152/ajpcell.00484.2025. Epub 2025 Jul 31.
Circadian rhythms are endogenous biological clocks that regulate physiology and behaviors, such as food intake, and are synchronized by the environmental light/dark cycle. The nucleus of the solitary tract (NTS) receives excitatory glutamatergic inputs from vagal afferent neurons that innervate the gastrointestinal tract and are sensitive to the gut peptide cholecystokinin (CCK), which is released following food intake to promote satiation. Previously, we observed that NTS membrane properties, neurotransmission, and action potential firings were all under circadian control. Although it is well established that the food intake varies with the light/dark cycle, circadian variations in the cellular actions of CCK on vagal afferent neurons remain unknown. Here, we test the extent to which CCK signaling on vagal afferents and the NTS changes as a function of time of day. We used RT-qPCR and functional cellular measurements to measure gene expression and responses to CCK across the time of day in rats. Although we confirmed the presence of rhythmic clock gene expression in vagal afferent neurons, we found that CCK1 receptors did not show diurnal rhythmicity. We also observed that CCK-induced calcium responses were consistent during the day and night in dissociated vagal afferent neurons. Similarly, CCK-driven increases in spontaneous glutamate release were also constant across the light cycle at the vagal afferent-NTS synapse. We conclude that vagal afferent CCK signaling remains constant across the light cycle, and CCK1 receptors provide a consistent point of reference independent of the time of day. Daily rhythms govern feeding and the processes of satiation conveyed by cholecystokinin acting on vagal afferent neurons. Yet, the putative changes in efficacy and direct cellular effects of CCK on vagal afferents across the time of day remain unknown. Here, we report constant CCK1 receptor expression and signaling in vagal afferents across the light cycle. This model indicates a fixed point of reference for CCK signaling in parallel to documented circadian changes in feeding neurocircuitry.
昼夜节律是调节生理和行为(如食物摄入)的内源性生物钟,并通过环境光/暗周期同步。孤束核(NTS)从支配胃肠道的迷走传入神经元接收兴奋性谷氨酸能输入,这些神经元对胆囊收缩素(CCK)敏感,CCK在食物摄入后释放以促进饱腹感。此前,我们观察到NTS的膜特性、神经传递和动作电位发放均受昼夜节律控制。虽然食物摄入量随光/暗周期变化已得到充分证实,但CCK对迷走传入神经元的细胞作用的昼夜变化仍不清楚。在此,我们测试了CCK在迷走传入神经和NTS上的信号传导随一天中时间的变化程度。我们使用逆转录定量聚合酶链反应(RT-qPCR)和功能性细胞测量来测量大鼠一天中不同时间对CCK的基因表达和反应。虽然我们证实了迷走传入神经元中存在节律性生物钟基因表达,但我们发现CCK1受体没有显示出昼夜节律性。我们还观察到,在解离的迷走传入神经元中,CCK诱导的钙反应在白天和晚上是一致的。同样,在迷走传入神经 - NTS突触处,CCK驱动的自发性谷氨酸释放增加在整个光周期中也保持恒定。我们得出结论,迷走传入神经的CCK信号在整个光周期中保持恒定,并且CCK1受体提供了一个与一天中的时间无关的一致参考点。日常节律控制着进食以及胆囊收缩素作用于迷走传入神经元所传达的饱腹感过程。然而,CCK在一天中不同时间对迷走传入神经的功效和直接细胞效应的假定变化仍不清楚。在此,我们报告了迷走传入神经在整个光周期中CCK1受体表达和信号传导保持恒定。该模型表明CCK信号传导有一个固定的参考点,与记录的进食神经回路中的昼夜变化并行。
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