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Scientists report capturing first image of memories being made

June 28, 2009
Courtesy McGill University
and World Science staff

Re­search­ers say they have cap­tured the first im­age of a mech­an­ism un­der­ly­ing long-term mem­o­ry forma­t­ion, called pro­tein transla­t­ion.

The find­ing pro­vides the first vis­u­al ev­i­dence that when a new mem­o­ry is formed, new pro­teins, types of large molecules, are pro­duced at syn­apses, or con­nec­tions be­tween nerve cells, ac­cord­ing to the sci­en­tists. 

The increase in green fluo­r­es­cence, in­di­cated by the ar­row­heads, re­pre­sents the im­ag­ing of lo­cal trans­la­tion at sy­n­apses dur­ing long-term plas­ti­city, re­search­ers say. (Cour­tesy Sci­ence)
The pro­cess, they ex­plained, boosts the strength of the con­nec­tion and re­in­forces the mem­o­ry.

The, study by re­search­ers at the Mont­real Neu­ro­lo­g­i­cal In­sti­tute and Hos­pi­tal, McGill Un­ivers­ity in Mont­real, and and Un­ivers­ity of Cal­i­for­nia, Los An­ge­les was pub­lished in the June 19 is­sue of the re­search jour­nal Sci­ence.

When con­sid­er­ing what might be go­ing on in the brain at a mo­lec­u­lar lev­el two prop­er­ties of mem­o­ry must be tak­en in­to ac­count, said Wayne Sossin, a neu­ro­sci­ent­ist at the in­sti­tute and and co-invest iga­tor in the stu­dy. First, be­cause a lot of in­forma­t­ion needs to be main­tained over a long time there must be some sta­bil­ity. Sec­ond, to al­low for learn­ing and adapta­t­ion the sys­tem al­so needs to be highly flex­i­ble. 

Most re­search has fo­cused on syn­apses which are the main site of ex­change and stor­age in the brain. They form a vast but al­so con­stantly fluc­tu­at­ing net­work of con­nec­tions whose abil­ity to change and adapt, called syn­ap­tic plas­ticity, may be the fun­da­men­tal ba­sis of learn­ing and mem­o­ry, ac­cord­ing to Sossin.

“But, if this net­work is con­stantly chang­ing, the ques­tion is how do mem­o­ries stay put, how are they formed? It has been known for some time that an im­por­tant step in long-term mem­o­ry forma­t­ion is ‘transla­t­ion,’ or the pro­duc­tion, of new pro­teins lo­cally at the syn­apse, strength­en­ing the syn­ap­tic con­nec­tion in the re­in­force­ment of a mem­o­ry, which un­til now has nev­er been im­aged,” said Sossin.

“Us­ing a transla­t­ional re­port­er, a flu­o­res­cent pro­tein that can be easily de­tected and tracked, we di­rectly vis­u­alized the in­creased lo­cal transla­t­ion, or pro­tein syn­the­sis, dur­ing mem­o­ry forma­t­ion. Im­por­tant­ly, this transla­t­ion was syn­apse-specific and it re­quired ac­tiva­t­ion of the post-syn­ap­tic cel­l,” that is, the cell re­ceiv­ing a sig­nal across the syn­apse, he added.

Thus “this step re­quired coop­era­t­ion be­tween the pre and post-syn­ap­tic com­part­ments, the parts of the two neu­rons [nerve cells] that meet at the syn­apse. Thus highly reg­u­lat­ed lo­cal transla­t­ion oc­curs at syn­apses dur­ing long-term plas­ticity.”

Long-term mem­o­ry and syn­ap­tic plas­ticity re­quire changes in gene ac­ti­vity and can oc­cur in a syn­apse-specific man­ner, the re­search­ers said. This study pro­vides ev­i­dence, they added, that a mech­an­ism be­hind this gene ac­tiva­t­ion dur­ing neu­ronal plas­ticity in­volves con­trolled pro­tein transla­t­ion at syn­apses. These find­ings will help of­fer in­sight in­to dis­eases in­volv­ing mem­o­ry im­pair­ment, Sossin and col­leagues pre­dicted.

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Researchers say they have captured the first image of a mechanism underlying long-term memory formation, called protein translation. The finding provides the first visual evidence that when a new memory is formed new proteins, types of large molecules, are produced at synapses, or connections between nerve cells, according to the scientists. The process, they explained, boosts the strength of the connection and reinforces the memory. The, study by researchers at the Montreal Neurological Institute and Hospital, McGill University in Montreal, and and University of California, Los Angeles was published in the June 19 issue of the research journal Science. When considering what might be going on in the brain at a molecular level two properties of memory must be taken into account, said Wayne Sossin, a neuroscientist at the institute and and co-investigator in the study. First, because a lot of information needs to be maintained over a long time there must be some stability. Second, to allow for learning and adaptation the system also needs to be highly flexible. For this reason, research has focused on synapses which are the main site of exchange and storage in the brain. They form a vast but also constantly fluctuating network of connections whose ability to change and adapt, called synaptic plasticity, may be the fundamental basis of learning and memory, according to Sossin. “But, if this network is constantly changing, the question is how do memories stay put, how are they formed? It has been known for some time that an important step in long-term memory formation is ‘translation,’ or the production, of new proteins locally at the synapse, strengthening the synaptic connection in the reinforcement of a memory, which until now has never been imaged,” said Sossin. “Using a translational reporter, a fluorescent protein that can be easily detected and tracked, we directly visualized the increased local translation, or protein synthesis, during memory formation. Importantly, this translation was synapse-specific and it required activation of the post-synaptic cell,” that is, the cell receiving a signal across the synapse, he added. Thus “this step required cooperation between the pre and post-synaptic compartments, the parts of the two neurons [nerve cells] that meet at the synapse. Thus highly regulated local translation occurs at synapses during long-term plasticity.” Long-term memory and synaptic plasticity require changes in gene activity and yet can occur in a synapse-specific manner, the researchers said. This study provides evidence, they added, that a mechanism behind this gene activation during neuronal plasticity involves controlled protein translation at synapses. These findings will help establish the molecular processes involved in long-term memory formation and offer insight into diseases involving memory impairment, Sossin and colleagues predicted.