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August 03, 2010

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Scientists report giving flies false memories

Oct. 15, 2009
Courtesy Cell Press
and World Science staff

Bi­ol­o­gists say they have giv­en flies mem­o­ries of a bad ex­pe­ri­ence they nev­er had, by ma­ni­pu­lat­ing the ac­ti­vity of in­di­vid­ual brain cells.

The find­ings may shed light on how learn­ing and mem­o­ries work in more com­plex or­gan­isms al­so, the sci­en­tists claim.

“We like to take seem­ingly lofty psy­cho­log­i­cal phe­nom­e­na and re­duce them to me­chan­ics, to see for ex­am­ple how the in­tel­li­gence needed to adapt to a chang­ing en­vi­ron­ment can be re­duced to phys­i­cal in­ter­ac­tions be­tween cells and molecules,” said Gero Mie­sen­böck of the Un­ivers­ity of Ox­ford, a mem­ber of the re­search group.

“The ques­tion is: how do you get in­tel­li­gence from parts that are un­in­tel­li­gent?”

The find­ings are de­scribed in the Oct. 16 is­sue of the re­search jour­nal Cell.

The back­ground to the study was that “flies have the abil­ity to learn, but the cir­cuits that in­struct mem­o­ry forma­t­ion were un­known,” Mie­sen­böck said. 

“We were able to pin the es­sen­tial com­po­nent down to 12 cells.” Those cells are suf­fi­cient to let the in­sect learn to as­so­ci­ate a par­tic­u­lar odor with some­thing bad, like an elec­tric shock, he ex­plained. The cells es­sen­tially cre­ate mem­o­ries that the fly then uses to avoid that odor. 

To pin­point the cells re­spon­si­ble for this mem­o­ry among thou­sands of cells in the fly brain, the re­search­ers used a tech­nique in which a flash of light is used to re­lease spe­cif­ic mo­le­cules from chem­i­cal “cages” in­side cer­tain cells. The mo­le­cules then stim­u­late an ac­ti­vity in those cells. 

An anal­o­gous situa­t­ion, said Mie­sen­böck, is that if you wanted to send a mes­sage only to cer­tain in­hab­i­tants of a city, you would give those you wanted to reach a ra­di­o tuned to the right fre­quen­cy and send the mes­sage pub­lic­ly, over the air­waves.

Miesen­böck said his team made some ed­u­cat­ed guesses about the parts of the brain that would be im­por­tant for the flies’ learn­ing task. From there, they were able to nar­row it down through ex­pe­ri­menta­t­ion to the 12-neuron brain cir­cuit. 

Re­mark­ably, stim­u­lat­ing just these neu­rons gives the flies a mem­o­ry of an un­pleas­ant event that nev­er oc­curred, he added.

Us­ing their ap­proach to “write di­rectly to mem­o­ry,” sci­en­tists can now ob­tain a lev­el of ev­i­dence about brain func­tion that was im­pos­si­ble be­fore, Mie­sen­böck said. He notes that neu­ro­sci­ence for a long time de­pended pri­marily on re­cord­ing brain ac­ti­vity and at­tempt­ing to cor­re­late it to per­cep­tions, ac­tions, and cog­ni­tion. But “it’s more pow­er­ful to seize con­trol of the rel­e­vant brain cir­cuits and pro­duce these states di­rectly,” he said.

Miesen­böck adds that the sim­ple brain of a fly likely can tell us much about how more com­plex brains work. “As a gen­er­al rule, bi­ol­o­gy tends to be con­ser­va­tive,” he said. “It’s rare that ev­o­lu­tion ‘in­vents’ the same pro­cess sev­er­al times.” And, he said, even sim­ple or­gan­isms may turn out to have a “sur­pris­ingly rich men­tal life.”

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Biologists say they have given flies memories of a bad experience they never had, by manipulating the activity of individual brain cells. The findings may shed light on how learning and memories work in more complex organisms also, the scientists claim. “We like to take seemingly lofty psychological phenomena and reduce them to mechanics, to see for example how the intelligence needed to adapt to a changing environment can be reduced to physical interactions between cells and molecules,” said Gero Miesenböck of the University of Oxford, a member of the research group. “The question is: how do you get intelligence from parts that are unintelligent?” The findings are described in the Oct. 16 issue of the research journal Cell. The background to the study was that “flies have the ability to learn, but the circuits that instruct memory formation were unknown,” Miesenböck said. “We were able to pin the essential component down to 12 cells.” Those cells are sufficient to let the insect learn to associate a particular odor with something bad, like an electric shock, he explained. The cells essentially create memories that the fly then uses to avoid that odor. To pinpoint the exact cells responsible for this memory among thousands in the fly brain, the researchers used a technique in which a flash of light is used to release specific molecules from chemical “cages” inside certain cells. The molecules then stimulate an activity in those neurons. An analogous situation, said Miesenböck, is that if you wanted to send a message only to certain inhabitants of a city, you would give those you wanted to reach a radio tuned to the right frequency and send the message publicly, over the airwaves. Miesenböck said his team made some educated guesses about the parts of the brain that would be important for the flies’ learning task. From there, they were able to narrow it down through experimentation to the 12-neuron brain circuit. Remarkably, stimulating just these neurons gives the flies a memory of an unpleasant event that never occurred, he added. Using their approach to “write directly to memory,” scientists can now obtain a level of evidence about brain function that was impossible before, Miesenböck said. He notes that neuroscience for a long time depended primarily on recording brain activity and attempting to correlate it to perceptions, actions, and cognition. “It’s more powerful to seize control of the relevant brain circuits and produce these states directly,” he said. Miesenböck adds that the simple brain of a fly likely can tell us much about how more complex brains work. “As a general rule, biology tends to be conservative,” he said. “It’s rare that evolution ‘invents’ the same process several times.” And, he said, even simple organisms may turn out to have a “surprisingly rich mental life.”