The body's internal clock helps to regulate a water-storing hormone¹ so that nightly dehydration² or trips to the toilet are not the norm, research suggests.

In an article published in Nature Neuroscience today, neurophysiologists Eric Trudel and Charles Bourque at the Research Institute of the McGill University Health Centre in Montreal, Canada, propose a mechanism³ by which the body's circadian system, or internal clock, controls water regulation1. By allowing cells that sense water levels to activate⁴ cells that release vasopressin, a hormone that instructs the body to store water, the circadian system keeps the body hydrated during sleep.

"We've known for years that there's a rhythm of vasopressin that gets high when you're sleeping. But no one knew how that occurred. And this group identified a very concrete physiological⁵ mechanism of how it occurs," says Christopher Colwell, a neuroscientist who studies sleep and circadian rhythms at the David Geffen School of Medicine at the University of California, Los Angeles.

The body regulates its water content mainly by balancing water intake⁶ through thirst with water loss through urine production. People don't drink during sleep, so the body has to minimize water loss to remain sufficiently⁷ hydrated. Scientists knew that low water levels excite a group of cells called osmosensory neurons, which direct another set of neurons to release vasopressin into the bloodstream. Vasopressin levels increase during sleep; clock neurons, meanwhile, get quieter.

Trudel and Bourque tested the idea that lower clock-neuron activity might allow osmosensory neurons to more easily activate vasopressin-releasing neurons, which would mean more water retention⁹ and less urine production during sleep.

To do this, they isolated¹⁰ thin slices of rat brain containing intact sensory⁸, vasopressin-releasing and clock neurons. Even when removed from the brain, clock neurons continue to mark time.

The duo then stimulated¹¹ the sensory neurons and recorded any electrical activity in the vasopressin-releasing neurons to monitor communication between the two cell groups. The researchers then moved on to look at the effect of the clock cells on this pathway. When they did not activate the clock cells during the 'sleep' part of their cycle, it was easier for the sensory cells to communicate with vasopressin-releasing cells. Conversely, when they activated¹² the clock cells, this communication decreased markedly.

The results suggest that clock cells function as a dimmer switch for water control. When their activity is high, they prevent sensory cells from instructing secretory¹³ cells to release vasopressin. Then, when clock cells are less active, sensory cells can easily instruct secretory cells to release vasopressin, ensuring that the body holds on to its water reserves.

Colwell points out that the study was done in rats, which are nocturnal. Although the vasopressin cycle and clock-neuron activity are similar in rats and humans, the question of whether the same mechanism occurs in animals that sleep at night remains¹⁴ to be answered.

"We show this for this one circuit, but it's possible that clock neurons regulate other circuits in a similar manner and this remains to be studied," says Bourque. He speculates that future studies might reveal whether the same mechanism regulates hunger, sleepiness and other aspects of physiology¹⁵ related to circadian rhythms.

自然》杂志新闻（NatureNews）安德鲁·贝内特·赫尔曼（AndrewBennett Hellman）

生物钟是控制身体水分流失的荷尔蒙调节开关。

大脑细胞使动物在睡觉期间保持水分，而不觉口渴。

研究显示，身体内部的生物钟帮助调节一种水分储存荷尔蒙，因此人晚上一般不会感到口渴或者频繁上厕所。

2月28日发表在《自然神经科学》杂志（Nature Neuroscience）上的一篇论文中，加拿大蒙特利尔麦吉尔大学健康中心研究所（Research Institute of the McGill University Health Centre）的神经生理学家埃里克·特鲁德尔（Eric Trudel）和查尔斯·布尔克（Charles Bourque）提出了一种机制，通过这种机制身体的昼夜系统（circadiansystem），或者说内部生物钟能够控制水分的调节。通过允许感知水含量的细胞去激活能够释放抗利尿激素（vasopressin）的细胞，抗利尿激素是一种指示身体进行储水的荷尔蒙，昼夜系统就能使身体在睡觉时储存水分（而不觉口渴）。

“多年来我们已经知道，当你在睡觉时抗利尿激素的水平会升高。但是没有人知道这是如何发生的。而这个研究团队提出了一种关于其如何发生的非常具体的生理机制，”神经科学家克里斯托弗·科尔韦尔（Christopher Colwell）说，他在加州大学洛杉矶分校（UCLA）大卫·格芬医学院（DavidGeffen School of Medicine）从事睡眠与昼夜节律的研究。

身体主要通过平衡因口渴而饮水与因产生尿液而排水来调节水含量。人们在睡觉时不会喝水，所以身体必须使水分流失最小化来保持充足的水分。科学家知道低含水量会激活一组被称为渗透感觉（osmosensory）神经元的细胞，它们能指示另一组神经元以释放抗利尿激素到血液中。在睡眠期间抗利尿激素水平增加；同时，生物钟神经元变得更加安静。

特鲁德尔和布尔克检验了这个想法，即更低的生物钟神经元活动可能允许渗透感觉神经元更容易激活抗利尿激素释放神经元，这将意味着在睡眠期间人体会保存更多的水并产生更少的尿液。

为了检验这个想法，他们将小白鼠的大脑分离成薄片，这些薄片仍然包含未受损伤的完整的感觉神经元、抗利尿激素释放神经元和生物钟神经元。即使当这些薄片从大脑里取出后，生物钟神经元仍然能够继续记录时间。

然后这两名研究者对感觉神经元施加刺激，并记录抗利尿激素释放神经元中的任何电活动来检测这两组细胞间的沟通。此后，研究者转而考察使用这种方法后生物钟神经元的效应。当他们未对处于昼夜周期中“睡眠”时期的生物钟细胞进行激活时，感觉细胞更容易与抗利尿激素释放细胞沟通。相反，当他们激活（睡眠时期的）生物钟细胞时，这种沟通明显下降。

这些结果指出了生物钟细胞作为身体水分控制开关的功能。当它们的活动很强时，它们阻止感觉细胞指示分泌细胞（secretory cell）去释放抗利尿激素。相反，当生物钟细胞激活水平比较弱时，感觉细胞能够更容易地指示分泌细胞释放抗利尿激素，以保证身体在睡眠时保持足够的蓄水量。

科尔韦尔指出这项研究是在小白鼠上进行的，而老鼠恰恰是夜间活动动物。虽然老鼠和人类体内的抗利尿激素释放周期和生物钟神经元活动都很相似，但是动物夜间睡眠期间是否都发生了相同的机制这个问题仍需回答。

“我们只是显示了这一个生物反馈回路的结论，但是可能生物钟神经元也以同样的方式调节其他的反馈回路，这仍需继续研究，”布尔克说。他预测未来的研究将可能揭示是否相同的机制也调节了饥饿、嗜睡以及与昼夜节律相关的其他生理问题。