Using optogenetics, researchers used pulses of light to prevent seizure-like activity in neurons. This is the first use of optogenetics to modulate seizure activity at the network level in human brain tissue. Because epilepsy is a disease of aberrant neuronal activity—an imbalance of excitation and inhibition—controlling neurons in the pathologic circuits of epilepsy could allow for control of the disease..

利用光遗传学，研究人员使用光脉冲来防止神经元中类似癫痫发作的活动。这是首次使用光遗传学在人脑组织的网络水平上调节癫痫发作活动。由于癫痫是一种神经元活动异常的疾病，癫痫病理回路中兴奋和抑制控制神经元的失衡可以控制疾病。。

The researchers used brain tissue that had been removed from epilepsy patients as part of their treatment. Eventually, they hope the technique will replace surgery to remove the brain tissue where seizures originate, providing a less invasive option for patients whose symptoms cannot be controlled with medication..

研究人员使用从癫痫患者身上切除的脑组织作为治疗的一部分。最终，他们希望这项技术将取代手术，切除癫痫发作的脑组织，为症状无法通过药物控制的患者提供一种侵入性较小的选择。。

This work is published in Nature Neuroscience in the paper, “Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices.”

The optogenetics method employed an AAV vector to deliver light-sensitive genes to neurons in the brain that can be switched on and off with pulses of light. More specifically, the slices were transduced with “AAV9 carrying an HcKCR1 transgene driven by a CAMK2A promoter and a fluorescent tag (enhanced yellow fluorescent protein (eYFP)).” HcKCR1 encodes a kalium channelrhodopsin which is a potassium-selective, light-sensitive ion channel that hyperpolarizes the neuronal membrane.

光遗传学方法使用AAV载体将光敏基因传递给大脑中的神经元，这些神经元可以通过光脉冲打开和关闭。更具体地说，切片用“携带由CAMK2A启动子和荧光标签（增强型黄色荧光蛋白（eYFP））驱动的HcKCR1转基因的AAV9”转导。“HcKCR1编码钾通道视紫红质，它是一种钾选择性的光敏离子通道，可使神经元膜超极化。

This reduces the probability of spiking when activated by 530 nm light..

这降低了被530 nm光激活时出现尖峰的可能性。。

This work is the first demonstration that optogenetics can be used to control seizure activity in living human brain tissue, and it opens the door to new treatments for other neurological diseases and conditions.

这项工作首次证明光遗传学可用于控制活体人脑组织的癫痫发作活动，并为其他神经系统疾病和病症的新疗法打开了大门。

“This represents a giant step toward a powerful new way of treating epilepsy and likely other conditions,” said Tomasz Nowakowski, PhD, an assistant professor of neurological surgery at the University of California, San Francisco (UCSF).

加州大学旧金山分校（UCSF）神经外科助理教授托马斯诺瓦科夫斯基（Tomasz Nowakowski）博士说：“这标志着朝着一种强大的治疗癫痫和其他疾病的新方法迈出了一大步。”。

To keep the tissue alive long enough to complete the study, which took several weeks, the researchers created an environment that mimics conditions inside the skull. The team hoped to use the light pulses to prevent the bursts by switching off neurons that contained light-sensitive proteins. The team needed to find a way to run their experiments without disturbing the tissue.

为了使组织存活足够长的时间以完成这项耗时数周的研究，研究人员创造了一个模拟颅骨内部条件的环境。该团队希望通过关闭含有光敏蛋白的神经元，利用光脉冲来防止爆发。该团队需要找到一种在不干扰组织的情况下进行实验的方法。

They designed a remote-control system to record the neurons’ electrical activity and deliver light pulses to the tissue..

他们设计了一个远程控制系统来记录神经元的电活动，并向组织传递光脉冲。。

“This was a very unique collaboration to solve an incredibly complex research problem,” said Mircea Teodorescu, PhD, an associate professor of electrical and computer engineering at UCSF. “The fact that we actually accomplished this feat shows how much farther we can reach when we bring the strengths of our institutions together.”.

加州大学旧金山分校电气与计算机工程副教授Mircea Teodorescu博士说：“这是一次非常独特的合作，可以解决一个极其复杂的研究问题。”。“我们实际上完成了这一壮举，这一事实表明，当我们将我们机构的优势结合在一起时，我们可以走得更远。”。

John Andrews, MD, a resident in neurosurgery at UCSF placed the tissue on a nutrient medium that resembles the cerebrospinal fluid that bathes the brain. David Schaffer, PhD, a biomolecular engineer at UC Berkeley, identified the AAV to deliver the genes. Teodorescu designed a remote-control system to record the neurons’ electrical activity and deliver light pulses to the tissue..

加州大学旧金山分校神经外科住院医师约翰·安德鲁斯（JohnAndrews）将组织置于营养培养基上，该培养基类似于沐浴大脑的脑脊液。加州大学伯克利分校的生物分子工程师DavidSchaffer博士确定了AAV可以传递基因。特奥多雷斯库设计了一个远程控制系统来记录神经元的电活动，并向组织传递光脉冲。。

The team demonstrated “AAV–mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions.” They could see which types of neurons—and how many of them—were needed to start a seizure.

该团队证明了“AAV介导的光遗传学降低了高密度微电极阵列上记录的在几种多动症激发条件下人类海马切片的网络放电率。”他们可以看到哪些类型的神经元以及需要多少神经元才能开始癫痫发作。

And they determined the lowest intensity of light needed to change the electrical activity of the neurons in live brain slices. The researchers could also see how interactions between neurons inhibited a seizure..

他们还确定了改变活脑切片中神经元电活动所需的最低光强度。研究人员还可以看到神经元之间的相互作用如何抑制癫痫发作。。

Edward Chang, MD, the chair of neurological surgery at UCSF, said these insights could revolutionize care for people with epilepsy. “We’ll be able to give people much more subtle, effective control over their seizures while saving them from such an invasive surgery,” he said.

加州大学旧金山分校神经外科主席爱德华·张医学博士表示，这些见解可能会彻底改变对癫痫患者的护理。他说：“我们将能够让人们更加微妙、有效地控制癫痫发作，同时使他们免于这种侵入性手术。”。

NewsAdeno associated viral vectorEpilepsyOptogenetics

新腺相关病毒载体pilepsyoptogenetics