The Science Behind the Nobel-Winning Technology That Controls Neurons With Light
The Karolinska Institute awarded the 2026 Nobel Prize in Medicine to researchers Karl Deisseroth of Stanford University, Peter Hegemann of Humboldt University in Berlin, and Georg Nagel of the University of Würzburg. Their discoveries led to the development of optogenetics, a technique where scientists can turn individual nerve cells on or off using beams of light.
卡罗林斯卡学院将2026年诺贝尔医学奖授予了斯坦福大学的卡尔·戴瑟罗斯(Karl Deisseroth)、柏林洪堡大学的彼得·黑格曼(Peter Hegemann)和维尔茨堡大学的格奥尔格·纳格尔(Georg Nagel)。他们的发现促成了光遗传学的发展,这是一种科学家可以利用光束开启或关闭单个神经细胞的技术。
According to Per Svenningsson, chair of the Nobel Committee for Medicine, “Optogenetics provides opportunities for mapping the brain in a way that we could once only dream of.” No other technique allows for such precise study of a living brain, helping researchers better understand the functions of our nervous systems as well as various neurological diseases and disorders.
诺贝尔医学委员会主席佩尔·斯文宁森(Per Svenningsson)表示:“光遗传学为绘制大脑图谱提供了我们曾经只能梦想的机会。”没有其他技术能对活体大脑进行如此精确的研究,这有助于研究人员更好地理解我们神经系统的功能以及各种神经系统疾病和紊乱。
But this prize is not just a celebration of neuroscience. It also serves as a triumphant example of what can happen when different disciplines of biology converge, as the findings that served as the basis for the development of optogenetics emerged from research in microbiology.
但这个奖项不仅仅是对神经科学的庆祝。它也是生物学不同学科融合所能产生结果的一个成功范例,因为作为光遗传学发展基础的发现源于微生物学研究。
At the end of the last century, Peter Hegemann began a series of studies to understand how the single-celled alga Chlamydomonas is able to detect and react to light. Previous research documented that Chlamydomonas has an “eye spot,” a small orange dot on its surface that contains a light-sensing molecule called retinal.
上世纪末,彼得·黑格曼开始了一系列研究,旨在了解单细胞藻类衣藻(Chlamydomonas)是如何探测光线并对其做出反应的。先前的研究记录显示,衣藻表面有一个“眼点”,这是一个含有视黄醛(一种光敏分子)的小橙色斑点。
Hegemann used tiny electrodes to measure the electrical signals generated by the alga and to expand our understanding of this structure’s rapid response. The scientist discovered that the organism was capable of producing an electrical impulse about 0.5 milliseconds after receiving light. This response time is 20 times faster than that of the human eye, whose light detection process takes at least 10 milliseconds.
黑格曼利用微小电极测量了藻类产生的电信号,并扩展了我们对该结构快速反应的理解。这位科学家发现,该生物在接收到光线后约0.5毫秒内就能产生电脉冲。这一反应时间比人眼快20倍,人眼的光探测过程至少需要10毫秒。
Hegemann suggested that light detection in the alga must be the result of a much simpler process than that identified in the human eye. In the early 1990s, he proposed that the eye spots contained a protein that both detected the light and responded to it, likely opening as a channel to let ions through. At the time, this hypothesis sparked controversy. Many ion channels had been documented up to that point, but none could respond to light on their own.
黑格曼认为,藻类的光探测过程一定比人眼中的过程简单得多。20世纪90年代初,他提出眼点中含有一种既能探测光线又能对其做出反应的蛋白质,它很可能作为一种通道打开,让离子通过。当时,这一假设引发了争议。尽管在那之前已经记录了许多离子通道,但没有一个能独立对光做出反应。
To test his theory, the scientist attempted to isolate the light-sensitive proteins from the eye spot. However, when removed from their natural environment, these proteins became unstable. Later, a group of Japanese researchers sequenced the complete DNA of Chlamydomonas, which allowed Hegemann’s team to identify two genes that would create proteins with the expected characteristics of a possible light-sensing channel.
为了验证他的理论,这位科学家试图从眼点中分离出光敏蛋白。然而,当这些蛋白质脱离其自然环境时,它们变得不稳定。后来,一组日本研究人员对衣藻的完整DNA进行了测序,这使得黑格曼的团队能够识别出两个基因,这些基因可以产生具有潜在光敏通道预期特征的蛋白质。
Georg Nagel took the next step of verifying the function of the genes. He introduced copies of each of the identified genes separately into different groups of frog eggs. The eggs began to produce the corresponding proteins, which eventually localized to the cell membranes. Nagel then turned on the lights.
格奥尔格·纳格尔采取了下一步行动,验证了这些基因的功能。他将每个已识别基因的副本分别引入到不同组的青蛙卵中。这些卵开始产生相应的蛋白质,并最终定位在细胞膜上。随后,纳格尔打开了灯。
Both proteins functioned as ion channels that opened when exposed to light. He named the genes channelrhodopsin-1 and channelrhodopsin-2. Further experiments showed the protein produced by this second gene—called ChR2 for short—opened especially quickly, the flow of ions occurring in just 0.2 milliseconds. It explained the extraordinary speed of the light reaction originally observed in Chlamydomonas.
这两种蛋白质都发挥了离子通道的作用,在接触光线时会打开。他将这些基因命名为通道视紫红质-1(channelrhodopsin-1)和通道视紫红质-2(channelrhodopsin-2)。进一步的实验表明,由第二个基因产生的蛋白质(简称ChR2)打开速度特别快,离子流动仅在0.2毫秒内发生。这解释了最初在衣藻中观察到的光反应的非凡速度。
When the researchers introduced the gene into mammalian cells—which do not normally respond to light—the cells generated an electrical signal when illuminated. This is what got the neuroscientists particularly excited.
当研究人员将该基因引入哺乳动物细胞(通常对光没有反应)时,这些细胞在受到光照时产生了电信号。这正是让神经科学家们感到特别兴奋的地方。
Ion channels are important across many types of cells, but they do some especially heavy lifting in our nervous systems. The electrical impulses that neurons use to communicate with one another, as well as other tissues in our body, are mediated by the flow of ions in and out of the cell. If you can control the ion channels, you can control the neuron.
离子通道在多种类型的细胞中都很重要,但它们在我们的神经系统中承担着尤为繁重的任务。神经元用于相互交流以及与我们体内其他组织交流的电脉冲,是由进出细胞的离子流介导的。如果你能控制离子通道,你就能控制神经元。
This is where Karl Deisseroth comes in. Deisseroth was searching for a method that would allow him to toggle the activity of specific nerve cells in a living brain. In his view, this tool could expand our understanding of brain functions and open new avenues for treating conditions such as depression and schizophrenia.
这就是卡尔·戴瑟罗斯发挥作用的地方。戴瑟罗斯一直在寻找一种方法,使他能够切换活体大脑中特定神经细胞的活动。在他看来,这种工具可以扩展我们对大脑功能的理解,并为治疗抑郁症和精神分裂症等疾病开辟新途径。
Following the discovery of ChR2, he asked Nagel for the DNA sequence so he could introduce it into rat nerve cells. The neurons, growing in dishes, produced ChR2 and, when illuminated with blue light, reacted immediately—sending an electrical impulse that propagated to other neurons. This result, obtained in 2005, was decisive in establishing ChR2 as a tool for neuroscience.
在发现ChR2后,他向纳格尔索要了DNA序列,以便将其引入大鼠神经细胞中。在培养皿中生长的神经元产生了ChR2,当用蓝光照射时,它们立即做出反应——发送了一个传播到其他神经元的电脉冲。这一2005年获得的结果,对于确立ChR2作为神经科学工具的地位具有决定性意义。
In the following years, Deisseroth, Hegemann, and Nagel collaborated to identify other proteins capable of activating or deactivating neurons using different wavelengths of light. With this toolkit, researchers can now design experiments where one group of neurons is turned on by one wavelength of light and another set of neurons is controlled by a different wavelength.
在接下来的几年里,戴瑟罗斯、黑格曼和纳格尔合作识别了其他能够利用不同波长的光来激活或抑制神经元的蛋白质。有了这个工具包,研究人员现在可以设计实验,其中一组神经元由一种波长的光开启,而另一组神经元则由另一种波长的光控制。
The term optogenetics was coined in 2006 and has since been implemented in a variety of studies. “Using optogenetics, researchers have been able to reveal neural circuits governing specific memories, feelings, and behaviors relevant for neurological and psychiatric disorders. In clinical medicine, researchers are using the method in attempts to restore sight in people with visual impairment,” the Nobel Assembly at the Karolinska Institute stated in a press release.
“光遗传学”(optogenetics)一词于2006年被创造出来,此后已被应用于各种研究中。卡罗林斯卡学院诺贝尔大会在新闻稿中表示:“利用光遗传学,研究人员已经能够揭示控制与神经和精神疾病相关的特定记忆、感觉和行为的神经回路。在临床医学中,研究人员正在使用这种方法尝试恢复视力受损者的视力。”
This story originally appeared on WIRED en Español and has been translated from Spanish.
本文最初发表于《连线》西班牙语版(WIRED en Español),并由西班牙语翻译而来。