REMEMBER your first kiss? Experiments in mice suggest that patterns of chemical "caps" on our DNA may be responsible for preserving such memories.

To remember a particular event, a specific sequence of neurons must fire at just the right time. For this to happen, neurons must be connected in a certain way by chemical junctions called synapses. But how they last over decades, given that proteins in the brain, including those that form synapses, are destroyed and replaced constantly, is a mystery.

Now Courtney Miller and David Sweatt of the University of Alabama in Birmingham say that long-term memories may be preserved by a process called DNA methylation - the addition of chemical caps called methyl groups onto our DNA.

Many genes are already coated with methyl groups. When a cell divides, this "cellular memory" is passed on and tells the new cell what type it is - a kidney cell, for example. Miller and Sweatt argue that in neurons, methyl groups also help to control the exact pattern of protein expression needed to maintain the synapses that make up memories.

They started by looking at short-term memories. When caged mice are given a small electric shock, they normally freeze in fear when returned to the cage. However, then injecting them with a drug to inhibit methylation seemed to erase any memory of the shock. The researchers also showed that in untreated mice, gene methylation changed rapidly in the hippocampus region of the brain for an hour following the shock. But a day later, it had returned to normal, suggesting that methylation was involved in creating short-term memories in the hippocampus (Neuron, DOI: 10.1016/j.neuron.2007.02.022).

To see whether methylation plays a part in the formation of long-term memories, Miller and Sweatt repeated the experiment, this time looking at the uppermost layers of the brain, called the cortex.

They found that a day after the shock, methyl groups were being removed from a gene called calcineurin and added to another gene. Because the exact pattern of methylation eventually stabilised and then stayed constant for seven days, when the experiment ended, the researchers say the methyl changes may be anchoring the memory of the shock into long-term memory, not just controlling a process involved in memory formation.

"We think we're seeing short-term memories forming in the hippocampus and slowly turning into long-term memories in the cortex," says Miller, who presented the results last week at the Society for Neuroscience meeting in Washington DC.

"The cool idea here is that the brain could be borrowing a form of cellular memory from developmental biology to use for what we think of as memory," says Marcelo Wood, who researches long-term memory at the University of California, Irvine.

還記得你的初吻嗎？通過(guò)老鼠身上的實(shí)驗(yàn)，我們發(fā)現(xiàn)DNA中的化學(xué)“磁帶”或許能為你記錄下這段記憶。

為了記起某件事情，一系列特定的神經(jīng)細(xì)胞會(huì)在適當(dāng)?shù)臅r(shí)間作出反應(yīng)。為了做到這點(diǎn)，神經(jīng)細(xì)胞必須通過(guò)叫做“神經(jīng)突觸”的化學(xué)接口以某種方式聯(lián)接起來(lái)。然而構(gòu)成神經(jīng)突觸的腦內(nèi)蛋白質(zhì)不斷地在更新?lián)Q代，那又是如何做到將記憶保存幾十年的呢？這是一個(gè)謎。

最近伯明翰阿拉巴馬大學(xué)的考特尼·米勒和大衛(wèi)·斯威特認(rèn)為，長(zhǎng)期記憶有可能是通過(guò)一個(gè)稱為DNA甲基化作用的過(guò)程而得到保存的，即是指在我們的DNA中加入甲基群來(lái)起到化學(xué)磁帶的作用。

許多基因外部都包有甲基群。當(dāng)細(xì)胞分裂的時(shí)候，它的“細(xì)胞記憶”就被傳遞給新生的細(xì)胞，好讓它記住自己是哪種類(lèi)型的細(xì)胞——比如說(shuō)腎細(xì)胞。米勒和斯威特稱，在神經(jīng)細(xì)胞中，甲基群也能夠控制蛋白質(zhì)對(duì)信息的傳遞，從而使得構(gòu)成記憶的神經(jīng)突觸得以保存。

一開(kāi)始他們從短期記憶著手進(jìn)行研究。對(duì)籠中的老鼠施加微小的電擊后，它們往往會(huì)對(duì)再次進(jìn)入籠中感到十分的恐慌。然而，在給它們注射了抑制甲基化作用的藥物后，它們對(duì)于電擊的記憶似乎就完全被消去了。此外研究者們證明，沒(méi)有注射過(guò)藥物的老鼠在遭到電擊后的一小時(shí)內(nèi)，它們大腦中海馬狀突起區(qū)域內(nèi)的基因中甲基發(fā)生著劇烈的變化，但經(jīng)過(guò)一天之后就恢復(fù)正常了。這說(shuō)明甲基化作用與海馬狀突起區(qū)域內(nèi)短期記憶的形成是有關(guān)連的。

為了探明甲基化作用對(duì)于長(zhǎng)期記憶的形成是否也有影響，米勒和斯威特重復(fù)了上面的實(shí)驗(yàn)。這次他們關(guān)注的是大腦活動(dòng)的最高級(jí)部位——大腦皮層。

他們發(fā)現(xiàn)老鼠在遭受電擊一天之后，神經(jīng)鈣蛋白基因中的甲基群就被轉(zhuǎn)移到了其它的基因中去。由于甲基化作用最終穩(wěn)定下來(lái)并且在接下來(lái)的七天內(nèi)都保持如此，實(shí)驗(yàn)結(jié)束后研究者們認(rèn)為甲基變化的作用可能在于將對(duì)于電擊的記憶轉(zhuǎn)化成長(zhǎng)期記憶固定下來(lái)，而不半單單是控制記憶形成的過(guò)程。

“我想我們所看到的，是海馬狀突起區(qū)域內(nèi)所形成的短期記憶逐漸轉(zhuǎn)化為大腦皮層中長(zhǎng)期記憶的過(guò)程”，米勒說(shuō)。在上周神經(jīng)系統(tǒng)科學(xué)學(xué)會(huì)在華盛頓舉行的會(huì)議上，他們公布了這一研究結(jié)果。

爾灣加利福尼亞大學(xué)的馬塞洛·伍德從事長(zhǎng)期記憶的研究。他認(rèn)為：“大腦有可能是采用了發(fā)生學(xué)中細(xì)胞記憶的形式，從而構(gòu)成我們所說(shuō)的記憶。這是一個(gè)十分有趣的想法。”