The suprachiasmatic nucleus (SCN) drives circadian rhythms in locomotion through coupled, single-cell oscillations. Global genetic deletion of the neuropeptide Vip or its receptor Vipr2 results in profound deficits in daily synchrony among SCN cells and daily rhythms in locomotor behavior and glucocorticoid secretion. To test whether this phenotype depends on vasoactive intestinal polypeptide (VIP) neurons in the SCN, we ablated VIP SCN neurons in vivo in adult male mice through Caspase3-mediated induction of the apoptotic pathway in cre-expressing VIP neurons. We found that ablation of VIP SCN neurons in adult mice caused a phenotype distinct from Vip- and Vipr2-null mice. Mice lacking VIP neurons retained rhythmic locomotor activity with a shortened circadian period, more variable onsets, and decreased duration of daily activity. Circadian hormonal outputs, specifically corticosterone rhythms, were severely dampened. In contrast, deletion of neonatal SCN VIP neurons dramatically reduced circadian gene expression in the cultured SCN, mimicking the effects of global deletion of Vip or Vipr2. These results suggest that SCN VIP neurons play a role in lengthening circadian period and stimulating the daily surge in glucocorticoids in adults and in synchronizing and sustaining daily rhythms among cells in the developing SCN.

视交叉上核 (SCN) 通过耦合的单细胞振荡驱动运动中的昼夜节律。神经肽Vip或其受体Vipr2 的全局基因缺失导致 SCN 细胞之间的日常同步性以及运动行为和糖皮质激素分泌的日常节律严重缺陷。为了测试这种表型是否依赖于 SCN 中的血管活性肠多肽 (VIP) 神经元，我们通过 Caspase3 介导的表达 cre 的 VIP 神经元中的凋亡途径诱导成年雄性小鼠体内的 VIP SCN 神经元。我们发现成年小鼠中 VIP SCN 神经元的消融导致了与Vip-和Vipr2-不同的表型空老鼠。缺乏 VIP 神经元的小鼠保留了节律性运动活动，昼夜节律缩短，发作更多变，日常活动持续时间减少。昼夜激素分泌，特别是皮质酮节律，受到严重抑制。相比之下，新生儿 SCN VIP 神经元的删除显着降低了培养的 SCN 中的昼夜节律基因表达，模拟了Vip或Vipr2的全局删除的影响。这些结果表明 SCN VIP 神经元在延长昼夜节律和刺激成人糖皮质激素的每日激增以及同步和维持发育中的 SCN 细胞之间的日常节律方面发挥作用。