In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which transmits circadian information to other brain regions and regulates the timing of sleep and wakefulness. Neurons in the lateral hypothalamus (LH), particularly those producing melanin-concentrating hormone (MCH)- and orexin are key regulators of sleep and wakefulness. Although the SCN receives non-photic input from other brain regions, the mechanisms of functional input from the LH to the SCN remain poorly understood. Here, we show that orexin and MCH peptides influence the circadian period within the SCN of both sexes. When these neurons are ablated, the circadian behavioral rhythms are lengthened under constant darkness. Using anterograde and retrograde tracing, we found that orexin and MCH neurons project to the SCN. Furthermore, the application of these peptides to cultured SCN slices shortened circadian rhythms and reduced intracellular cAMP levels. Additionally, pharmacological reduction of intracellular cAMP levels similarly shortened the circadian period in SCN slices. These findings suggest that orexin and MCH peptides from the LH contribute to the modulation of the circadian period in the SCN.Significance statement In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, where it regulates circadian rhythms, including sleep and wakefulness. The SCN receives both neuronal and humoral input signals from external brain regions, which can modify circadian rhythms within the SCN. While several brain regions that project to the SCN have been anatomically identified, the specific regions, neuronal cell types, and neurotransmitters that influence SCN circadian rhythms remain largely uncharacterized. This study identifies two neuronal populations within the lateral hypothalamus that project to the SCN and modulate the circadian period.

中文翻译：

---

从下丘脑外侧到视交叉上核的神经肽能输入改变了小鼠的昼夜节律。


在哺乳动物中，中央生物钟位于下丘脑的视交叉上核 （SCN），它将昼夜节律信息传递到其他大脑区域并调节睡眠和觉醒的时间。下丘脑外侧 （LH） 中的神经元，尤其是那些产生黑色素浓缩激素 （MCH） 和食欲素的神经元，是睡眠和觉醒的关键调节因子。尽管 SCN 接收来自其他大脑区域的非光输入，但从 LH 到 SCN 的功能输入机制仍然知之甚少。在这里，我们表明食欲素和 MCH 肽影响两性 SCN 内的昼夜节律。当这些神经元被消融时，昼夜节律在持续的黑暗中会延长。使用顺行和逆行追踪，我们发现食欲素和 MCH 神经元投射到 SCN。此外，将这些肽应用于培养的 SCN 切片可缩短昼夜节律并降低细胞内 cAMP 水平。此外，细胞内 cAMP 水平的药理学降低同样缩短了 SCN 切片中的昼夜节律。这些发现表明，来自 LH 的食欲素和 MCH 肽有助于调节 SCN 中的昼夜节律。意义声明 在哺乳动物中，中央生物钟位于下丘脑的视交叉上核 （SCN），在那里它调节昼夜节律，包括睡眠和觉醒。SCN 接收来自外部大脑区域的神经元和体液输入信号，这可以改变 SCN 内的昼夜节律。虽然已经从解剖学上确定了投射到 SCN 的几个大脑区域，但影响 SCN 昼夜节律的特定区域、神经元细胞类型和神经递质在很大程度上仍未表征。 本研究确定了下丘脑外侧的两个神经元群，它们投射到 SCN 并调节昼夜节律。