The need to sleep is sensed and discharged in a poorly understood process that is homeostatically controlled over time. In flies, different contributions to this process have been attributed to peripheral ppk and central brain neurons, with the former serving as hypothetical inputs to the sleep homeostat and the latter reportedly serving as the homeostat itself. Here we re-evaluate these distinctions in light of new findings using female flies. First, activating neurons targeted by published ppk and brain drivers elicits similar phenotypes, namely, sleep deprivation followed by rebound sleep. Second, inhibiting activity or synaptic output with one type of driver suppresses sleep homeostasis induced using the other type of driver. Third, drivers previously used to implicate central neurons in sleep homeostasis unexpectedly also label ppk neurons. Fourth, activating only this subset of colabeled neurons is sufficient to elicit sleep homeostasis. Thus, many published contributions of central neurons to sleep homeostasis can be explained by previously unrecognized expression of brain drivers in peripheral ppk neurons, most likely those in the legs, which promote walking. Last, we show that activation of certain non-ppk neurons can also induce sleep homeostasis. Notably, axons of these as well as ppk neurons terminate in the same ventral brain region, suggesting that a previously undefined neural circuit element of a sleep homeostat may lie nearby.

SIGNIFICANCE STATEMENT The biological needs that sleep fulfills are unknown, but they are reflected by the ability of an animal to compensate for prior sleep loss in a process called sleep homeostasis. Researchers have searched for the neural circuitry that comprises the sleep homeostat so that the information it conveys can shed light on the nature of sleep need. Here we demonstrate that neurons originating outside of the brain are responsible for phenotypes previously attributed to the proposed central brain sleep homeostat in flies. Our results support a revised neural circuit model for sensing and discharging sleep need in which peripheral inputs connect to a sleep homeostat through previously unrecognized neural circuit elements in the ventral brain.

睡眠的需要是在一个鲜为人知的过程中被感知和释放的，这个过程是随着时间的推移而被稳态控制的。在果蝇中，对这一过程的不同贡献归因于外周 ppk 和中央大脑神经元，前者充当睡眠稳态器的假设输入，据报道后者充当稳态器本身。在这里，我们根据使用雌性果蝇的新发现重新评估这些区别。首先，激活已发表的 ppk 和大脑驱动程序所针对的神经元会引发类似的表型，即睡眠剥夺，然后是反弹睡眠。其次，用一种类型的驱动程序抑制活动或突触输出会抑制使用另一种类型的驱动程序引起的睡眠稳态。第三，以前用来暗示睡眠稳态中枢神经元的驱动程序出人意料地也标记了 ppk 神经元。第四，仅激活这部分共标记神经元就足以引发睡眠稳态。因此，许多已发表的中枢神经元对睡眠稳态的贡献可以用以前未被识别的外周 ppk 神经元中大脑驱动器的表达来解释，很可能是促进行走的腿部神经元。最后，我们表明某些非 ppk 神经元的激活也可以诱导睡眠稳态。值得注意的是，这些轴突以及 ppk 神经元终止于同一腹侧大脑区域，这表明之前未定义的睡眠稳态器神经回路元件可能位于附近。许多已发表的中枢神经元对睡眠稳态的贡献可以用以前未被识别的外周 ppk 神经元中大脑驱动器的表达来解释，很可能是促进行走的腿部神经元。最后，我们表明某些非 ppk 神经元的激活也可以诱导睡眠稳态。值得注意的是，这些轴突以及 ppk 神经元终止于同一腹侧大脑区域，这表明之前未定义的睡眠稳态器神经回路元件可能位于附近。许多已发表的中枢神经元对睡眠稳态的贡献可以用以前未被识别的外周 ppk 神经元中大脑驱动器的表达来解释，很可能是促进行走的腿部神经元。最后，我们表明某些非 ppk 神经元的激活也可以诱导睡眠稳态。值得注意的是，这些轴突以及 ppk 神经元终止于同一腹侧大脑区域，这表明之前未定义的睡眠稳态器神经回路元件可能位于附近。

意义声明睡眠满足的生物学需求是未知的，但它们反映在动物在称为睡眠稳态的过程中补偿先前睡眠损失的能力上。研究人员一直在寻找构成睡眠稳态器的神经回路，以便它传达的信息可以揭示睡眠需求的本质。在这里，我们证明起源于大脑外部的神经元负责先前归因于所提出的果蝇中枢大脑睡眠稳态器的表型。我们的结果支持用于感知和释放睡眠需求的修订神经回路模型，其中外围输入通过腹侧大脑中以前未被识别的神经回路元件连接到睡眠稳态器。