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
據(jù)2005年4月8日出版的《細(xì)胞》雜志的一篇文章說(shuō),，耶魯大學(xué)醫(yī)學(xué)院的科研人員發(fā)現(xiàn)對(duì)果蠅進(jìn)行某些精神控制的一種方法，通過(guò)觸動(dòng)安裝在果蠅中樞神經(jīng)系統(tǒng)內(nèi)的基因“遙控”，能使果蠅跳躍,、拍打翅膀或按指令飛行。文章作者說(shuō),，該發(fā)現(xiàn)代表神經(jīng)科學(xué)從被動(dòng)觀察轉(zhuǎn)向主動(dòng)操縱行為的重大進(jìn)步,。
遙控基于這樣一種想法：可以給某些神經(jīng)元裝上分子“接收器”，使它們能辨認(rèn)像激光脈沖之類的外界信號(hào)并將其轉(zhuǎn)成神經(jīng)元活動(dòng)特有的電信號(hào),。為實(shí)現(xiàn)這一想法,，蘇珊娜·利馬和格羅·米森博克設(shè)計(jì)了一個(gè)觸發(fā)的“鎖與鑰匙”系統(tǒng)――“鎖”就是經(jīng)基因編碼能在目標(biāo)神經(jīng)元中顯示的接收器，“鑰匙”就是與“鎖”系在一起并能開(kāi)動(dòng)“鎖”的分子,，激光則是將“鑰匙”插入“鎖”的觸發(fā)器,。
他們將能使帶電粒子穿過(guò)細(xì)胞膜的離子通道（或稱成孔蛋白）作為鎖，將能夠開(kāi)啟離子通道的小分子三磷酸腺苷（ATP）作為鑰匙,。為使ATP能與離子通道一直系在一起并適時(shí)提前啟動(dòng)神經(jīng)元的活動(dòng),，利馬和米森博克用另一種化合物將ATP關(guān)起來(lái)，而激光則可以移去該化合物,。
米森博克說(shuō),，實(shí)驗(yàn)最困難的部分在于決定遙控系統(tǒng)應(yīng)瞄準(zhǔn)哪些特定神經(jīng)元。他們決定瞄準(zhǔn)果蠅的大神經(jīng)系統(tǒng)（giant fiber system）,。因?yàn)榇笊窠?jīng)系統(tǒng)控制逃生,、跳躍、飛行等非常具體的定型動(dòng)作,，所以,，他們推斷,，如果對(duì)果蠅的大神經(jīng)系統(tǒng)進(jìn)行遙控后,，果蠅出現(xiàn)這些行為，則說(shuō)明他們?cè)O(shè)計(jì)的系統(tǒng)有用,。
他們對(duì)果蠅實(shí)施了基因工程,，在其大神經(jīng)系統(tǒng)中顯示出離子通道，然后將微量ATP注射到果蠅體內(nèi),，再將它們關(guān)在一個(gè)玻璃半球內(nèi),，用紫外波長(zhǎng)的激光照射。結(jié)果，這些果蠅開(kāi)始做出伸腿,、跳躍,、開(kāi)啟并快速拍打翅膀等一連串的逃生動(dòng)作。
他們得出的結(jié)論是,，大神經(jīng)系統(tǒng)內(nèi)部的遙控在63％的時(shí)間有作用,，而其它受大神經(jīng)系統(tǒng)控制的神經(jīng)元內(nèi)的遙控則在82％的時(shí)間有作用。利馬和米森博克還給多巴胺能神經(jīng)元裝備了遙控,，結(jié)果加快了果蠅的活動(dòng)并改變了它們的飛行路線,。米森博克說(shuō)，這些觸發(fā)行為的持續(xù)時(shí)間為幾秒到幾分,，這取決于遙控所激活的神經(jīng)回路是否有反饋環(huán),。
美國(guó)耶魯大學(xué)的科學(xué)家們?nèi)涨氨硎荆麄兛梢杂眉す?ldquo;遙控”果蠅,，使其跳躍,、行走或是拍打翅膀，而這項(xiàng)研究的最終結(jié)果則可能對(duì)人們更好地了解人類暴飲暴食的行為和暴力行為有所幫助,。
據(jù)美聯(lián)社4月8日?qǐng)?bào)道,，耶魯大學(xué)的科學(xué)家們表示，利用激光刺激果蠅特殊的腦細(xì)胞,，他們可以讓果蠅完成跳躍,、行走、拍打翅膀和飛行等動(dòng)作,。他們還說(shuō),，如果刺激到恰當(dāng)?shù)纳窠?jīng)細(xì)胞，即使是無(wú)頭的果蠅也能對(duì)這種刺激作出反應(yīng),?？茖W(xué)家認(rèn)為，這項(xiàng)研究最終能幫助人們識(shí)別與人類精神失常,、過(guò)量飲食和暴力行為有關(guān)的細(xì)胞及其特性,。
耶魯大學(xué)的細(xì)胞生物學(xué)副教授Gero Miesenbock表示，如果這一過(guò)程能在老鼠身上復(fù)制,，研究人員或許能夠更好地了解導(dǎo)致某些失常行為的細(xì)胞的活躍性,。他說(shuō)：“最終，這將對(duì)了解人類精神失常起到至關(guān)重要的作用,。”
