"Long before it's in the papers"
January 27, 2015


Scientists hijack brain cells to remote-control worms

Sept. 24, 2012
Courtesy of Harvard University
and World Science staff

Us­ing la­sers, sci­en­tists say they have man­aged to take over an an­i­mal’s brain, make the crea­ture turn any way they want, and even plant false ideas, fool­ing it in­to think­ing food is near.

Re­search­ers from Har­vard Uni­vers­ity and from the How­ard Hughes Med­i­cal In­sti­tute in New York took con­trol of Cae­nor­hab­di­tis el­e­gans – ti­ny, trans­par­ent worms – by ma­ni­pu­lat­ing nerve cells in the worm equi­va­lent of the brain.

The work is im­por­tant be­cause “if we can un­der­stand sim­ple nerv­ous sys­tems to the point of com­pletely con­trolling them, then it may be a pos­si­bil­ity that we can gain a com­pre­hen­sive un­der­standing of more com­plex sys­tems,” said Har­vard’s Sha­rad Ra­ma­na­than, one of the in­ves­ti­ga­tors.

“We can make [the worm] turn left, we can make it turn right, we can make it go in a loop, we can make it think there is food near­by,” Ra­ma­na­than said. “We want to un­der­stand the brain of this an­i­mal… com­pletely and es­sen­tially turn it in­to a vi­deogame, where we can con­trol all of its be­hav­iors.”

The find­ings are de­scribed in the Sept. 23 is­sue of the re­search jour­nal Na­ture.

C. el­e­gans is a fairly sim­ple crea­ture, with just 302 neu­rons, or nerve cells, pro­cess­ing in­forma­t­ion. These are mostly found in a struc­ture called the head gan­glia, its ver­sion of the brain.

Past re­search has gleaned a lot of in­forma­t­ion by de­stroy­ing in­di­vid­ual brain cells to learn what these were do­ing, Ra­ma­na­than said. But “the ques­tion we were try­ing to an­swer was: In­stead of break­ing the sys­tem to un­der­stand it, can we es­sen­tially hi­jack the key neu­rons that are suf­fi­cient to con­trol be­hav­ior and use these neu­rons to force the an­i­mal to do what we wan­t?”

Us­ing ge­net­ic tools, re­search­ers en­gi­neered worms whose neu­rons gave off flu­o­res­cent light, al­low­ing them to be tracked dur­ing ex­pe­ri­ments. Re­search­ers al­so al­tered genes in the worms to make neu­rons sen­si­tive to light, mean­ing they could be ac­tivated with pulses of la­ser light.

The larg­est chal­lenges, Ra­ma­na­than re­called, came in de­vel­op­ing hard­ware that could track the worms and tar­get the cor­rect neu­ron in a frac­tion of a sec­ond.

“The goal is to ac­tivate only one neu­ron,” he ex­plained. “That’s chal­leng­ing be­cause the an­i­mal is mov­ing, and the neu­rons are densely packed near its head, so the chal­lenge is to ac­quire an im­age of the an­i­mal, pro­cess that im­age, iden­ti­fy the neu­ron, track the an­i­mal, po­si­tion your la­ser and shoot the par­tic­u­lar neu­ron – and do it all in 20 millisec­onds, or about 50 times a sec­ond. The en­gi­neer­ing chal­lenges in­volved seemed in­sur­mount­a­ble when we start­ed.”

But Askin Ko­cabas, a post-doctoral fel­low at Har­vard work­ing on the proj­ect, “found ways to overcome the­se,” he added.

The sci­en­tists eventually de­vel­oped a sys­tem that uses a mov­a­ble ta­ble to keep the crawl­ing worm cen­tered be­neath a cam­era and la­ser. Cus­tom-built com­put­er hard­ware and soft­ware plays a key role and is de­signed to en­sure the sys­tem works at the req­ui­site speeds.

The end re­sult, he said, was a sys­tem ca­pa­ble of not only con­trolling the worms’ be­hav­ior, but their senses. In one test de­scribed in the pa­per, re­search­ers were able to use the sys­tem to trick a wor­m’s brain in­to be­liev­ing food was near­by, caus­ing it to make a bee­line to­ward the im­ag­i­nary meal.

Ra­manathan and his team plan to ex­plore what oth­er be­hav­iors the sys­tem can con­trol in C. el­e­gans. Oth­er ef­forts in­clude de­sign­ing new cam­er­as and com­put­er hard­ware with the goal of speed­ing up the sys­tem from 20 millisec­onds to one. The in­creased speed is expected to al­low them to test the sys­tem in more com­plex an­i­mals, such as anoth­er com­mon test or­gan­ism, the ze­bra­fish.

* * *

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Using lasers, scientists say they have managed to take over an animal’s brain, make it turn any way they want, and even plant false ideas, fooling the creature into thinking food is near. Researchers from Harvard University and from the Howard Hughes Medical Institute in New York took control of Caenorhabditis elegans – tiny, transparent worms – by manipulating neurons in the worms’ “brains.” The work is important because “if we can understand simple nervous systems to the point of completely controlling them, then it may be a possibility that we can gain a comprehensive understanding of more complex systems,” said Harvard’s Sharad Ramanathan, one of the investigators. “We can make [the worm] turn left, we can make it turn right, we can make it go in a loop, we can make it think there is food nearby,” Ramanathan said. “We want to understand the brain of this animal… completely and essentially turn it into a video game, where we can control all of its behaviors.” The findings are described in the Sept. 23 issue of the journal Nature. C. elegans is a relatively simple creature, with just 302 neurons, or nerve cells, processing information in its brain. “This gives us a framework to think about neural circuits, how to manipulate them, which circuit to manipulate and what activity patterns to produce in them,” Ramanathan added. Past research has gleaned a lot of information by destroying individual brain cells to learn what these were doing, he went on. But “the question we were trying to answer was: Instead of breaking the system to understand it, can we essentially hijack the key neurons that are sufficient to control behavior and use these neurons to force the animal to do what we want?” Using genetic tools, researchers engineered worms whose neurons gave off fluorescent light, allowing them to be tracked during experiments. Researchers also altered genes in the worms to made neurons sensitive to light, meaning they could be activated with pulses of laser light. The largest challenges, Ramanathan recalled, came in developing hardware that could track the worms and target the correct neuron in a fraction of a second. “The goal is to activate only one neuron,” he explained. “That’s challenging because the animal is moving, and the neurons are densely packed near its head, so the challenge is to acquire an image of the animal, process that image, identify the neuron, track the animal, position your laser and shoot the particular neuron – and do it all in 20 milliseconds, or about 50 times a second. The engineering challenges involved seemed insurmountable when we started.” But Askin Kocabas, a post-doctoral fellow at Harvard working on the project, “found ways to overcome these,” he added. The scientists eventually developed a system that uses a movable table to keep the crawling worm centered beneath a camera and laser. Custom-built computer hardware and software plays a key role and is designed to ensure the system works at the requisite speeds. The end result, he said, was a system capable of not only controlling the worms’ behavior, but their senses. In one test described in the paper, researchers were able to use the system to trick a worm’s brain into believing food was nearby, causing it to make a beeline toward the imaginary meal. Ramanathan and his team plan to explore what other behaviors the system can control in C. elegans. Other efforts include designing new cameras and computer hardware with the goal of speeding up the system from 20 milliseconds to one. It’s thought the increased speed would allow them to test the system in more complex animals, such as another common test organism, the zebrafish.