The hypothalamic suprachiasmatic nuclei (SCN) are the principal mammalian circadian timekeeper, co-ordinating organism-wide daily and seasonal rhythms. To achieve this, cell-autonomous circadian timing by the ~20,000 SCN cells is welded into a tight circuit-wide ensemble oscillation. This creates essential, network-level emergent properties of precise, high-amplitude oscillation with tightly defined ensemble period and phase. Although synchronised, regional cell groups exhibit differentially phased activity, creating stereotypical spatiotemporal circadian waves of cellular activation across the circuit. The cellular circuit pacemaking components that generate these critical emergent properties are unknown. Using intersectional genetics and real-time imaging, we show that SCN cells expressing vasoactive intestinal polypeptide (VIP) or its cognate receptor, VPAC2, are neurochemically and electrophysiologically distinct, but together they control de novo rhythmicity, setting ensemble period and phase with circuit-level spatiotemporal complexity. The VIP/VPAC2 cellular axis is therefore a neurochemically and topologically specific pacemaker hub that determines the emergent properties of the SCN timekeeper.

下丘脑上视交叉核（SCN）是主要的哺乳动物生物钟，负责协调整个生物体的日常和季节性节律。为此，将约20,000个SCN单元的单元自主生物钟定时焊接到整个电路范围内的紧密整体振荡中。这将创建精确的，高振幅振荡的网络级紧急特性，并严格定义了合奏周期和相位。尽管是同步的，但区域性细胞群却表现出不同的阶段性活动，从而在整个电路中产生了典型的时空昼夜节律性细胞激活波。产生这些关键紧急特性的蜂窝电路起搏组件是未知的。使用交叉遗传学和实时成像，我们发现表达血管活性肠多肽（VIP）或其同源受体VPAC2的SCN细胞在神经化学和电生理学上是不同的，但它们共同控制了新生的节律性，设定了整体周期和相位，并具有电路级的时空复杂性。因此，VIP / VPAC2细胞轴是神经化学和拓扑特定的起搏器枢纽，它决定了SCN计时器的紧急特性。