Researchers use laser light to remote control flies
April 07, 2005
Yale University School of Medicine researchers have found a way to exercise a little mind control over fruit flies, making the flies jump, beat their wings, and fly on command by triggering genetic "remote controls" that the scientists designed and installed in the insects' central nervous systems, according to a new report in the 8 April issue of the journal Cell.
Susana Lima and Gero Miesenbock hope that the remote control system will provide a valuable way to study how nerve-cell activity and connections are related to specific behaviors, from simple movements to more complex behaviors like learning, aggression, and even abstract thought.
The ability to control specific groups of neurons without implanting electrodes in the brain or using similarly invasive techniques "would represent a significant step in moving neuroscience from passive observation…to active and predictive manipulation of behavior," the Cell authors write.
Miesenbцck also says "one could use this method to restore neural signals that have been lost" due to injury or disease, such as in spinal cord trauma, although he notes that the possibility is "far-fetched" at the moment.
The remote control is based on the idea that specific nerve cells could be equipped with molecular "receivers" that allow them to recognize an outside signal like a laser light pulse and translate that signal into the electrical signals characteristic of nerve-cell activity.
To accomplish this, Miesenbцck and Lima devised a triggered molecular lock and key system, where the "lock" was the receiver genetically encoded to be expressed in the target neurons, the "key" was the molecule that would bind to and activate the lock, and laser light was the trigger that brought the key to the lock.
For the lock, the researchers used an ion channel, or a pore-forming protein that allows charged particles to pass through a cell membrane. The small molecule ATP activates the ion channel chosen by the researchers, so ATP became the key. To keep the ATP from binding to the ion channel and jump-starting the nerve cell's activity before the proper moment, Lima and Miesenbцck caged the ATP with other chemical compounds that could be removed by the laser light.
Miesenbцck says one of the most difficult parts of the experiment was deciding which particular nerve cells to target with the remote control system. "To ascertain that the system actually worked, it wasn't clear how we could measure activation in the neurons in moving, freely behaving organisms," he explains.
The breakthrough, he says, came when they decided to target a small set of nerve cells in the fly called the giant fiber system. The giant fiber system controls very specific, stereotypical movements such as escape movements, jumping, and the beginnings of flight. If the flies engaged in these behaviors after the giant fiber neurons had been outfitted and "operated" with the remote control, Miesenbцck and Lima reasoned, they could be sure that their system was working.
After genetically engineering the flies to express the ion channel in the giant fiber system cells and using the tiniest of injections to place the caged ATP inside the flies, the researchers shone a ultraviolet-wavelength laser in brief, millisecond pulses at the flies trapped inside a glass-domed arena. On command, the flies began a series of escape movements--extending their legs, jumping, and opening and rapidly flapping their wings.
The laser-triggered remote controls in the giant fiber system worked about 63 percent of the time, while remote controls placed in other nerve cells that were targets of the giant fiber system worked 82 percent of the time, the researchers concluded. Lima and Misenbцck also equipped another set of nerve cells called dopaminergic neurons with the remote controls, boosting the flies' activity levels and changing their flight paths.
Misenbцck says the triggered behaviors can last seconds or continue for minutes, depending on whether the neural circuit activated by the remote control has feedback loops that keep the circuit. "In the case of the flight circuits," he says, "it is like pushing a swing. One initial kick and it keeps swinging back and forth for a while."
Source: Cell Press
据2005年4月8日出版的《细胞》杂志的一篇文章说，耶鲁大学医学院的科研人员发现对果蝇进行某些精神控制的一种方法，通过触动安装在果蝇中枢神经系统内的基因“遥控”，能使果蝇跳跃、拍打翅膀或按指令飞行。文章作者说，该发现代表神经科学从被动观察转向主动操纵行为的重大进步。
遥控基于这样一种想法：可以给某些神经元装上分子“接收器”，使它们能辨认像激光脉冲之类的外界信号并将其转成神经元活动特有的电信号。为实现这一想法，苏珊娜·利马和格罗·米森博克设计了一个触发的“锁与钥匙”系统――“锁”就是经基因编码能在目标神经元中显示的接收器，“钥匙”就是与“锁”系在一起并能开动“锁”的分子，激光则是将“钥匙”插入“锁”的触发器。
他们将能使带电粒子穿过细胞膜的离子通道（或称成孔蛋白）作为锁，将能够开启离子通道的小分子三磷酸腺苷（ATP）作为钥匙。为使ATP能与离子通道一直系在一起并适时提前启动神经元的活动，利马和米森博克用另一种化合物将ATP关起来，而激光则可以移去该化合物。
米森博克说，实验最困难的部分在于决定遥控系统应瞄准哪些特定神经元。他们决定瞄准果蝇的大神经系统（giant fiber system）。因为大神经系统控制逃生、跳跃、飞行等非常具体的定型动作，所以，他们推断，如果对果蝇的大神经系统进行遥控后，果蝇出现这些行为，则说明他们设计的系统有用。
他们对果蝇实施了基因工程，在其大神经系统中显示出离子通道，然后将微量ATP注射到果蝇体内，再将它们关在一个玻璃半球内，用紫外波长的激光照射。结果，这些果蝇开始做出伸腿、跳跃、开启并快速拍打翅膀等一连串的逃生动作。
他们得出的结论是，大神经系统内部的遥控在63％的时间有作用，而其它受大神经系统控制的神经元内的遥控则在82％的时间有作用。利马和米森博克还给多巴胺能神经元装备了遥控，结果加快了果蝇的活动并改变了它们的飞行路线。米森博克说，这些触发行为的持续时间为几秒到几分，这取决于遥控所激活的神经回路是否有反馈环。
美国耶鲁大学的科学家们日前表示，他们可以用激光“遥控”果蝇，使其跳跃、行走或是拍打翅膀，而这项研究的最终结果则可能对人们更好地了解人类暴饮暴食的行为和暴力行为有所帮助。
据美联社4月8日报道，耶鲁大学的科学家们表示，利用激光刺激果蝇特殊的脑细胞，他们可以让果蝇完成跳跃、行走、拍打翅膀和飞行等动作。他们还说，如果刺激到恰当的神经细胞，即使是无头的果蝇也能对这种刺激作出反应。科学家认为，这项研究最终能帮助人们识别与人类精神失常、过量饮食和暴力行为有关的细胞及其特性。
耶鲁大学的细胞生物学副教授Gero Miesenbock表示，如果这一过程能在老鼠身上复制，研究人员或许能够更好地了解导致某些失常行为的细胞的活跃性。他说：“最终，这将对了解人类精神失常起到至关重要的作用。”
