人為什么需要睡眠？為了遺忘

Over the years, scientists have come up with a lot of ideas about why we sleep.

關(guān)于我們?yōu)槭裁匆X(jué)，多年來(lái)，科學(xué)家提出了很多想法。

Some have argued that it’s a way to save energy. Others have suggested that slumber provides an opportunity to clear away the brain’s cellular waste. Still others have proposed that sleep simply forces animals to lie still, letting them hide from predators.

有些人認(rèn)為這是一種節(jié)約能量的方法。其他人提出，睡眠為大腦提供了清除細(xì)胞廢物的機(jī)會(huì)。還有一些人認(rèn)為，睡眠只是迫使動(dòng)物靜靜地躺下來(lái)，讓它們可以躲過(guò)捕食者。

A pair of papers published on Thursday in the journal Science offer evidence for another notion: We sleep to forget some of the things we learn each day.

周四在《科學(xué)》(Science)期刊上發(fā)表的兩篇論文為另一個(gè)觀念提供了證據(jù)：我們睡覺(jué)是為了忘記每天所學(xué)到的一些東西。

In order to learn, we have to grow connections, or synapses, between the neurons in our brains. These connections enable neurons to send signals to one another quickly and efficiently. We store new memories in these networks.

為了學(xué)習(xí)，我們必須增加大腦神經(jīng)元之間的連接，或者叫突觸。這些連接使神經(jīng)元能夠快速有效地在彼此之間發(fā)送信號(hào)。我們就是在這些網(wǎng)絡(luò)之中存儲(chǔ)新的記憶。

In 2003, Giulio Tononi and Chiara Cirelli, biologists at the University of Wisconsin-Madison, proposed that synapses grew so exuberantly during the day that our brain circuits got “noisy.” When we sleep, the scientists argued, our brains pare back the connections to lift the signal over the noise.

2003年，威斯康星大學(xué)麥迪遜分校的生物學(xué)家朱利奧·托諾尼(Giulio Tononi)和基婭拉·奇雷利(Chiara Cirelli)提出，突觸在白天生長(zhǎng)得非常激烈，令大腦電路變得“嘈雜”。當(dāng)我們睡覺(jué)時(shí),大腦得以減少連接，這樣真正的信號(hào)才可以超過(guò)噪聲。

In the years since, Dr. Tononi and Dr. Cirelli, along with other researchers, have found a great deal of indirect evidence to support the so-called synaptic homeostasis hypothesis.

在此之后的幾年里，托諾尼博士和奇雷利博士與其他研究者發(fā)現(xiàn)了大量間接證據(jù)，支持這一所謂的突觸自穩(wěn)態(tài)假說(shuō)。

It turns out, for example, that neurons can prune their synapses — at least in a dish. In laboratory experiments on clumps of neurons, scientists can give them a drug that spurs them to grow extra synapses. Afterward, the neurons pare back some of the growth.

比如，事實(shí)證明，神經(jīng)元可以修剪它們的突觸——至少是在實(shí)驗(yàn)室里。在對(duì)神經(jīng)元叢進(jìn)行實(shí)驗(yàn)室實(shí)驗(yàn)時(shí)，科學(xué)家給它們一種藥物，刺激它們生長(zhǎng)額外的突觸。之后，神經(jīng)元削減了一些生長(zhǎng)。

Other evidence comes from the electric waves released by the brain. During deep sleep, the waves slow down. Dr. Tononi and Dr. Cirelli have argued that shrinking synapses produce this change.

其他證據(jù)來(lái)自大腦釋放的電波。在深度睡眠期間，電波減慢。 托諾尼博士和奇雷利博士認(rèn)為，這種變化是由突觸縮小帶來(lái)的。

Four years ago, Dr. Tononi and Dr. Cirelli got a chance to test their theory by looking at the synapses themselves. They acquired a kind of deli slicer for brain tissue, which they used to shave ultrathin sheets from a mouse’s brain.

四年前，托諾尼博士和奇雷利博士得以通過(guò)觀察突觸本身來(lái)檢驗(yàn)他們的理論。他們獲得了一種用于腦組織的切片機(jī)，用它從小鼠的大腦上得到超薄切片。

Luisa de Vivo, an assistant scientist working in their lab, led a painstaking survey of tissue taken from mice, some awake and others asleep. She and her colleagues determined the size and shape of 6,920 synapses in total.

該實(shí)驗(yàn)室的助理科學(xué)家路易莎·德·維沃(Luisa de Vivo)對(duì)這些從小鼠大腦取出的組織進(jìn)行了精心研究，一些小鼠是醒著的，其他一些處于睡眠狀態(tài)。她和同事們確定了6920個(gè)突觸的大小和形狀。

The synapses in the brains of sleeping mice, they found, were 18 percent smaller than in awake ones. “That there’s such a big change over all is surprising,” Dr. Tononi said.

他們發(fā)現(xiàn)，睡眠小鼠腦中的突觸比清醒小鼠的突觸小18%。“整體而言，那個(gè)巨大的變化頗為驚人，”托諾尼博士說(shuō)。

The second study was led by Graham H. Diering, a postdoctoral researcher at Johns Hopkins University. Dr. Diering and his colleagues set out to explore the synaptic homeostasis hypothesis by studying the proteins in mouse brains. “I’m really coming at it from this nuts-and-bolts place,” Dr. Diering said.

第二項(xiàng)研究由約翰霍普金斯大學(xué)博士后研究員格雷厄姆·H·迪林(Graham H. Diering)領(lǐng)導(dǎo)。迪林博士和同事們通過(guò)研究小鼠腦中的蛋白質(zhì)來(lái)探索突觸自穩(wěn)態(tài)假說(shuō)。“我真的是從這種細(xì)節(jié)出發(fā)來(lái)研究這個(gè)問(wèn)題的，”迪林博士說(shuō)。

In one experiment, Dr. Diering and his colleagues created a tiny window through which they could peer into mouse brains. Then he and his colleagues added a chemical that lit up a surface protein on brain synapses.

在一個(gè)實(shí)驗(yàn)中，迪林博士和同事們創(chuàng)建了一個(gè)小窗口，通過(guò)它可以窺看小鼠的大腦。然后，他和同事們?cè)谛∈蟠竽X內(nèi)添加了一種化學(xué)物質(zhì)，能夠點(diǎn)亮腦突觸上的表面蛋白。

Looking through the window, they found that the number of surface proteins dropped during sleep. That decline is what you would expect if the synapses were shrinking.

透過(guò)窗口，他們發(fā)現(xiàn)，在睡眠期間突觸表面蛋白的數(shù)量下降。如果突觸縮小，這種下降就應(yīng)該會(huì)出現(xiàn)。

Dr. Diering and his colleagues then searched for the molecular trigger for this change. They found that hundreds of proteins increase or decrease inside of synapses during the night. But one protein in particular, called Homer1A, stood out.

迪林博士和同事們隨后開(kāi)始尋找這種變化的分子觸發(fā)因素。他們發(fā)現(xiàn)，在突觸內(nèi)，有數(shù)百種蛋白質(zhì)在夜間增加或減少。但有一種名為Homer1A的蛋白質(zhì)格外突出。

In earlier experiments on neurons in a dish, Homer1A proved to be important for paring back synapses. Dr. Diering wondered if it was important in sleep, too.

在對(duì)神經(jīng)元進(jìn)行的早期實(shí)驗(yàn)室實(shí)驗(yàn)中，Homer1A被證明在突觸減少過(guò)程中發(fā)揮了重要作用。迪林博士想知道它是否在睡眠中也很重要。

To find out, he and his colleagues studied mice genetically engineered so that they couldn’t make Homer1A proteins. These mice slept like ordinary mice, but their synapses didn’t change their proteins like the ones in ordinary mice. 為了發(fā)現(xiàn)這一點(diǎn)，他和同事研究了經(jīng)基因工程改造、不能制造Homer1A蛋白的小鼠。這些小鼠可以像普通小鼠一樣睡覺(jué)，但是它們的突觸不像在普通小鼠中那樣改變其蛋白質(zhì)。

Dr. Diering’s research suggests that sleepiness triggers neurons to make Homer1A and ship it into their synapses. When sleep arrives, Homer1A turns on the pruning machinery.

迪林博士的研究表明，困倦引發(fā)神經(jīng)元制造Homer1A，并將其運(yùn)送到突觸。當(dāng)睡眠開(kāi)始時(shí)，Homer1A也打開(kāi)了它的修剪機(jī)制。

To see how this pruning machinery affects learning, the scientists gave regular mice a memory test. They put the animals in a room where they got a mild electric shock if they walked over one section of the floor.

為了觀察這種修剪機(jī)制如何影響學(xué)習(xí)，科學(xué)家對(duì)普通小鼠進(jìn)行了記憶測(cè)試。他們把這些動(dòng)物放在一個(gè)房間里，如果它們走到地板的某一部分，就會(huì)受到輕微的電擊。

That night, the scientists injected a chemical into the brains of some of the mice. The chemical had been shown to block neurons in dishes from pruning their synapses.

當(dāng)天晚上，科學(xué)家將一種化學(xué)物質(zhì)注入若干小鼠的腦中。在實(shí)驗(yàn)室中，這種化學(xué)物質(zhì)已被證明可以阻止神經(jīng)元減少其突觸。

The next day, the scientists put all the mice back in the chamber they had been in before. Both groups of mice spent much of the time frozen, fearfully recalling the shock.

第二天，科學(xué)家把所有小鼠都放回之前所在的房間。兩組小鼠大部分時(shí)間都是一動(dòng)不動(dòng)，恐懼地回憶起電擊的記憶。

But when the researchers put the mice in a different chamber, they saw a big difference. The ordinary mice sniffed around curiously. The mice that had been prevented from pruning their brain synapses during sleep, on the other hand, froze once again.

但當(dāng)研究人員把老鼠放入不同的房間，他們看到了很大的區(qū)別。普通組的老鼠好奇地到處嗅著。另一邊，在睡眠期間被阻止減少大腦突觸的小鼠再次一動(dòng)不動(dòng)。

Dr. Diering thinks that the injected mice couldn’t narrow their memories down to the particular chamber where they had gotten the shock. Without nighttime pruning, their memories ended up fuzzy.

迪林博士認(rèn)為，受注射的小鼠不能把記憶縮小到它們?cè)馐茈姄舻奶囟ǚ块g范圍內(nèi)。沒(méi)有夜間的修剪，它們的記憶最后變得模糊。

In their own experiment, Dr. Tononi and his colleagues found that the pruning didn’t strike every neuron. A fifth of the synapses were unchanged. It’s possible that these synapses encode well-established memories that shouldn’t be tampered with.

在他們自己的實(shí)驗(yàn)中，托諾尼博士和同事們發(fā)現(xiàn)，修剪并不是針對(duì)每個(gè)神經(jīng)元。1/5的突觸沒(méi)有改變。有可能這些突觸之中編碼了已經(jīng)良好地建立起來(lái)、且不應(yīng)被修改的記憶。

“You can forget in a smart way,” Dr. Tononi said.

“你可以用一種聰明的方式來(lái)忘記，”托諾尼博士說(shuō)。

Other researchers cautioned that the new findings weren’t definitive proof of the synaptic homeostasis hypothesis.

其他研究者警告說(shuō)，新的發(fā)現(xiàn)并不能為突觸自穩(wěn)態(tài)假說(shuō)提供決定性的證據(jù)。

Marcos G. Frank, a sleep researcher at Washington State University in Spokane, said that it could be hard to tell whether changes to the brain at night were caused by sleep or by the biological clock. “It’s a general problem in the field,” he said.

華盛頓州立大學(xué)斯波坎分校的睡眠問(wèn)題研究者馬科斯·G·弗蘭克(Marcos G. Frank)說(shuō)，很難判斷大腦夜間的變化是由睡眠還是生物鐘引起的。“這是該領(lǐng)域的一個(gè)普遍問(wèn)題，”他說(shuō)。

Markus H. Schmidt, of the Ohio Sleep Medicine Institute, said that while the brain might prune synapses during sleep, he questioned whether this was the main explanation for why sleep exists.

俄亥俄睡眠醫(yī)學(xué)研究所(Ohio Sleep Medicine Institute)的馬庫(kù)斯·H·施密特(Markus H. Schmidt)說(shuō)，雖然大腦可能在睡眠期間修剪突觸，但他質(zhì)疑這一點(diǎn)是否是睡眠存在的主要原因。

“The work is great,” he said of the new studies, “but the question is, is this a function of sleep or is it the function?”

“這項(xiàng)工作很好，”他談起這項(xiàng)新研究時(shí)說(shuō)，“但問(wèn)題是，這是睡眠的功能之一，還是它的主要功能?”

Many organs, not just the brain, seem to function differently during sleep, Dr. Schmidt pointed out. The gut appears to make many new cells, for example.

不僅大腦，許多器官在睡眠時(shí)的功能似乎都不一樣，施密特博士指出。比如腸道似乎就會(huì)產(chǎn)生許多新的細(xì)胞。

Dr. Tononi said that the new findings should prompt a look at what current sleeping drugs do in the brain. While they may be good at making people sleepy, it’s also possible that they may interfere with the pruning required for forming memories.

托諾尼博士說(shuō)，新的發(fā)現(xiàn)可以促使人們審視目前的睡眠藥物在大腦中發(fā)揮什么作用。雖然它們可以讓人們感到困意，但它們也可能干擾形成記憶所需的突觸修剪。

“You may actually work against yourself,” Dr. Tononi said.

“你可能其實(shí)是在損害自己，”托諾尼博士說(shuō)。

In the future, sleep medicines might precisely target the molecules involved in sleep, ensuring that synapses get properly pruned.

在將來(lái)，睡眠藥物或許可以精確瞄準(zhǔn)參與睡眠的分子，確保突觸得到適當(dāng)?shù)男藜簟?/p>

“Once you know a little bit of what happens at the ground-truth level, you can get a better idea of what to do for therapy,” Dr. Tononi said.

“一旦你知道一點(diǎn)基本事實(shí)層面發(fā)生的情況，就可以得到更好的治療思路，”托諾尼博士說(shuō)。