爱思英语编者按:斯坦福大学的研究人员使用光来影响小白鼠的大脑,让一只患有帕金森症的小白鼠重新站立起来,甚至是重新走路。他们把这项技术称之为Optogenetics(光遗传学)。
Restoring lost memories
恢复丢失的记忆

Total recall
完整恢复
 
Missing memories have been restored in mice with Alzheimer’s disease
已经恢复痴呆症老鼠丢失的记忆
 
Remembering in a new light
记忆的曙光
1SOME mice can easily remember where they hide food, but not those genetically engineered to develop Alzheimer’s disease. Like humans they become forgetful. By the time these mice are seven months old they are unable to remember, for example, which arm of a maze they have explored before. Two months later, their brains are riddled with amyloid beta, the protein “plaques” that also characterise the latter stage of the disease in humans.
 
老鼠能轻易记起它们把食物藏在哪儿,但通过基因工程而患有痴呆症的老鼠却不能。它们和人类一样健忘。这些老鼠七个月大的时候就记不住,比如去过迷宫的哪条路。2个月之后,大脑就充满了β-淀粉样蛋白,这些蛋白质斑点同样是痴呆症病人晚期的特征。
 
2Now researchers have managed to restore memories to mice with Alzheimer’s. This helps provide more evidence about how memories are lost during the early stages of the disease and may point to how, some time in the future, those memories might be brought back.
 
现在研究者成功恢复了痴呆症老鼠的记忆。这提供了痴呆症早期是如何丢失记忆的线索,以及在未来记忆怎样被恢复的关键。
 
3Susumu Tonegawa and his colleagues at the Massachusetts Institute of Technology used a technique known as optogenetics, which activates clusters of neurons by shining light on them. As they report in Nature, the researchers prepared seven-month-old Alzheimer’s mice by injecting a harmless virus into the rodents’ dentate gyrus, a part of the hippocampus that helps to store fearful memories. The virus contains a gene for channelrhodopsin-2, a light-sensitive protein which forms pores in the cell membranes of neurons infected with the virus. These pores are closed in the dark, but open in response to blue light, flooding neurons with positively charged ions. The resulting pulse of current makes the neurons fire. During their experiments, the researchers were able to illuminate the infected neurons of the mice using optical fibres implanted in their brains.
 
麻省理工学院的利根川进和同事用一种“光遗传学”的技术,用光照刺激神经元集群。正如他们在《自然》上发表的那样,研究人员将一种无害病毒注射到预先准备的七个月大痴呆症老鼠的啮齿动物齿状回区,这个区域是海马体内帮助存储害怕记忆的一部分。病毒含有光敏感通道的基因,产生的光敏感蛋白能在被病毒感染的神经元细胞膜上形成通道。这些通道在无光照时是关闭的,但对蓝光起反应并打开,使神经元充满正离子。产生的电流脉冲使神经元产生电流。在实验中,研究人员能用光纤植入老鼠大脑来刺激感染的神经元。
 
4Using a standard lab test of memory, a mouse was placed in a box and given a small electrical shock to its feet. Normal mice remember this and freeze in fear if put back in the box the following day, but mice with Alzheimer’s scamper about unfazed. Yet when the researchers stimulated the dentate gyrus of these mice with blue light, they also froze, suggesting that they were now able to recall the original shock.
 
用一个标准的实验室记忆测试,一只老鼠被放在盒子里面并对它的脚给予微小电击。如果接下来几天把它放进盒子里,正常老鼠会记住并且由于害怕而呆住不动,痴呆症老鼠则不受影响活蹦乱跳。但当研究人员用蓝光刺激这些痴呆症老鼠的海马体时,它们一样会呆住不动,这表明它们能记起最初的电击感受。
 
5Holding on to a fearful memory in the long term, however, requires the brain to strengthen the nerve connections (synapses) that link memory of the box to experience of the shock. This process, known as long-term potentiation, goes awry in the brains of Alzheimer’s patients. Consistent with this idea, the Alzheimer’s mice did not freeze when placed in the box but only when their neurons were illuminated.
 
可是要长时间保持住害怕记忆,要求大脑加强神经联系(突触)来连结盒子里的电击实验的记忆。这个过程,叫做长时程增强,没能在痴呆症老鼠大脑里顺利进行。和这想法一致的是,把痴呆症老鼠放在盒子里,仅仅照射神经元,老鼠并没有呆住不动。
 
6To help the Alzheimer’s mice consolidate and keep their memory of the electric shock, the team flashed their dentate gyrus with blue light at 100 hertz, a frequency known to induce long-term potentiation. After this the Alzheimer’s mice froze in the box for at least six consecutive days, suggesting they were able to remember the shock themselves.
 
为了帮助痴呆症老鼠巩固和保持它们对电击的记忆,团队用100赫兹的蓝光照射它们的齿状回,这个频率能诱导长时程增强。这之后老鼠连续六天呆在盒子里不动,表明它们能记住电击感受。
 
7Work by other groups has suggested that in its early stages, Alzheimer’s principally damages the brain’s ability to process and store memories. This new work, however, indicates that it is the brain’s ability to retrieve memories that is impaired. The distinction is far from an academic one. If memories are garbled before they are stored, they are lost for ever. But if Dr Tonegawa is right, then memories are correctly preserved in the brains of Alzheimer’s patients. That means it may be possible to rescue them—perhaps by adapting optogenetics for use in human sufferers. That remains a distant possibility for now.
 
其他团队的工作早就表明在早期阶段,痴呆症主要破坏大脑加工和存储记忆的能力。然而这项新工作显示这正是大脑恢复受损记忆的能力。区别远大于理论。如果记忆在存储前就被篡改,那这段记忆就永远丢失了。但如果利根博士是对的,那段记忆被正确保留在痴呆症患者的大脑里。意味着有可能通过对人类患者适应光遗传学来恢复它们。
 
8But there is a more immediate consequence of the work for the estimated 40m people with the disease. Electrical stimulation of large areas of the brain of Alzheimer’s patients is already being tried, using electrodes implanted in the skull. But Dr Tonegawa’s team found that stimulating neurons in the dentate gyrus other than those directly involved with holding the fear memory prevented Alzheimer’s mice from remembering their shocks in the long term. That suggests that unless the technique can be refined, deep-brain stimulation may not be effective.
 
但这有一个更直接的调查结果,估计有4千万人患有痴呆症。用电极植入头脑里来对痴呆症病人大脑大区域电刺激也准备好被尝试。但利根博士的团队发现刺激齿状回去神经元而不是保持住害怕记忆,因为这会阻止痴呆症老鼠长时间记忆电击感受。这说明除非技术能够进步,深度大脑刺激可能无效。
From the print edition: Science and technology
 
 
译注
 
【海马体】主要负责记忆和学习,日常生活中的短期记忆都储存在海马体中,如果一个记忆片段,比如一个电话号码或者一个人在短时间内被重复提及的话海马体就会将其转存入大脑皮层,成为永久记忆。海马区可分为:齿状回(dentate gyrus)、海马、下托(subiculum)、前下托(presubiculum)、傍下托(parasubiculum)、内嗅皮质(entorhinal cortex)。
【脉冲】指电平状态突变,既可以是突然升高,也可以是突然降低.瞬间突然变化,作用时间极短的电压或电流称为脉冲信号.
【长时程增强(LTP)】是发生在两个神经元信号传输中的一种持久的增强现象,能够同步的刺激两个神经元。这是与突触可塑性--突触改变强度的能力相关的几种现象之一。由于记忆被认为是由突触强度的改变来编码的,LTP被普遍视为构成学习与记忆基础的主要分子机制之一。