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August 03, 2010

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Scientists create “memories” in isolated brain slices

Dec. 27, 2009
Courtesy Case West­ern Re­serve Un­ivers­ity
and World Science staff

Re­search­ers re­port that they cre­at­ed ap­par­ent “mem­o­ries” with­in slices of ro­dent brains kept alive in the lab­o­r­a­to­ry.

The find­ings are pub­lished in the Feb­ru­ary is­sue of the jour­nal Na­ture Neu­ro­sci­ence.

Neu­ro­sci­en­tists of­ten clas­si­fy mem­o­ry in­to three types: de­clar­a­tive mem­o­ry, such as stor­ing facts or re­mem­ber­ing spe­cif­ic events; pro­ce­du­ral mem­o­ry, such as learn­ing how to play the pia­no or shoot bas­ket­balls; and work­ing mem­o­ry, a type of short-term stor­age like re­mem­ber­ing a phone num­ber.

In the stu­dy, Ben Strow­bridge and Phil­lip La­ri­mer of Case West­ern Re­serve Un­ivers­ity in Cleve­land aimed to iden­ti­fy the brain cir­cuits be­hind work­ing mem­o­ry.

Us­ing iso­lat­ed pieces of ro­dent brain tis­sue, La­ri­mer found a way to rec­re­ate a type of work­ing mem­o­ry in the lab. He was stu­dying a type of brain cell, or neu­ron, called mossy cells, which are of­ten dam­aged in peo­ple with ep­i­lep­sy and are part of a struc­ture in the brain called the hip­po­cam­pus. 

“See­ing the mem­o­ry deficits that so many peo­ple with ep­i­lep­sy suf­fer from led me to won­der if there might be a fun­da­men­tal con­nec­tion be­tween hip­po­cam­pal mossy cells and mem­o­ry cir­cuits,” said La­ri­mer.

Mossy cells are un­usu­al be­cause they main­tain much of their nor­mal ac­ti­vity even when kept alive in thin brain slices. The spon­ta­ne­ous elec­tri­cal ac­ti­vity La­ri­mer and Strow­bridge found in mossy cells was crit­i­cal to their dis­cov­ery of mem­o­ry traces in this brain re­gion.

When stim­u­lat­ing elec­trodes were in­sert­ed in the brain slice the spon­ta­ne­ous ac­ti­vity in the mossy cells re­mem­bered which elec­trode had been ac­tivated, the re­searchers re­ported. The “mem­o­ries” lasted about 10 sec­onds, about as long as many types of work­ing mem­o­ries stud­ied in peo­ple.

“This is the first time an­y­one has stored in­forma­t­ion in spon­ta­ne­ously ac­tive pieces of mam­ma­li­an brain tis­sue. It is probably not a co­in­ci­dence that we were able to show this mem­o­ry ef­fect in the hip­po­cam­pus, the brain re­gion most as­so­ci­at­ed with hu­man mem­o­ry,” said Strow­bridge.

The sci­en­tists meas­ured the fre­quen­cy of syn­ap­tic in­puts—or the strength of the brain’s elec­tri­cal sig­nal­s—onto the mossy cells to de­ter­mine wheth­er or not the hip­po­cam­pus had re­tained mem­o­ry.

“Mem­ory was not ev­i­dent in one cell but it was ev­i­dent in a popula­t­ion of cells,” said Strow­bridge. 

“Like our own mem­o­ries, the mem­o­ries we cre­at­ed in iso­lat­ed brain slices were stored in many dif­fer­ent neu­rons or cells, that’s why we had to watch sev­er­al dif­fer­ent cells to see the stored in­forma­t­ion,” added Strow­bridge. 

Larimer and Strow­bridge al­so said they found the brain cir­cuit that ena­bled the hip­po­cam­pus to re­mem­ber which in­put path­way had been ac­tivated. The mem­o­ry ef­fect, they ex­plained, oc­curred thanks to a rare type of brain cell called sem­i­lu­nar gran­ule cells, de­scribed in 1893 by the fa­ther of neu­ro­sci­ence, the Spaniard Ramón y Ca­jal. But the cells have been little stu­died since then. The sem­i­lu­nar gran­ule cells have an un­usu­al form of per­sist­ent ac­ti­vity, al­low­ing them to main­tain mem­o­ry and con­nect to the mossy cells, ac­cord­ing to the group.

* * *

Researchers report that they apparently created “memories” within brain slices kept alive in the laboratory. The findings are published in the February issue of the journal Nature Neuroscience. Neuroscientists often classify human memory into three types: declarative memory, such as storing facts or remembering specific events; procedural memory, such as learning how to play the piano or shoot basketballs; and working memory, a type of short-term storage like remembering a phone number. In the study, Ben Strowbridge and Phillip Larimer of Case Western Reserve University in Cleveland aimed to identify the brain circuits behind working memory. Using isolated pieces of rodent brain tissue, Larimer found a way to recreate a type of working memory in the lab. He was studying a type of brain cell, or neuron, called mossy cells, which are often damaged in people with epilepsy and are part of a structure in the brain called the hippocampus. “Seeing the memory deficits that so many people with epilepsy suffer from led me to wonder if there might be a fundamental connection between hippocampal mossy cells and memory circuits,” said Larimer. Mossy cells are unusual because they maintain much of their normal activity even when kept alive in thin brain slices. The spontaneous electrical activity Larimer and Strowbridge found in mossy cells was critical to their discovery of memory traces in this brain region. When stimulating electrodes were inserted in the brain slice the spontaneous activity in the mossy cells remembered which electrode had been activated. The memory in vitro lasted about 10 seconds, about as long as many types of working memories studied in people. “This is the first time anyone has stored information in spontaneously active pieces of mammalian brain tissue. It is probably not a coincidence that we were able to show this memory effect in the hippocampus, the brain region most associated with human memory,” said Strowbridge. The scientists measured the frequency of synaptic inputs—or the strength of the brain’s electrical signals—onto the mossy cells to determine whether or not the hippocampus had retained memory. “Memory was not evident in one cell but it was evident in a population of cells,” said Strowbridge. “Like our own memories, the memories we created in isolated brain slices were stored in many different neurons or cells, that’s why we had to watch several different cells to see the stored information,” added Strowbridge. Larimer and Strowbridge also found the brain circuit that enabled the hippocampus to remember which input pathway had been activated. The memory effect, they explained, occurred because of a rare type of brain cell called semilunar granule cells, described in 1893 by the father of neuroscience, Ramón y Cajal. The semilunar granule cells have an unusual form of persistent activity, allowing them to maintain memory and connect to the mossy cells, according to the group. That finding was the foundation for the new study. The semilunar granule cells remained an obscurity for more than a century until Strowbridge’s group rediscovered them in a paper they published in 2007, according to Strowbridge and colleagues.