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When Nader presented his work in 2001 to a crowded lecture hall at the annual meeting of the Society for Neuroscience, the field’s premier academic gathering, he faced outright disbelief from some leaders in the field. “It caught the attention of lots of other neuro­scientists, because some had taken the view that once consolidation had been completed, it couldn’t be dislodged,” says David Riccio, an experimental psychologist at Kent State University in Ohio, whose own research in the 1970s had challenged the consolidation model.

It makes sense that the brain, in order to take in and store new information, would need to have some flexibility in the way it stores old memories. But does this really mean that when an old memory is recalled, the brain must dismantle the synaptic structure underlying the memory and then form it again? “Reconsolidation strikes me as a woefully inefficient way to make memory work,” says Ralph Miller, a behavioral neuroscientist at the State University of New York at Binghamton, who was also involved in the 1960s consolidation debate. “My own best guess is that every time we recall a memory, we lay down new versions.” In this model, the existing memories would remain intact, but they would be integrated with the new ones or superseded by them–meaning that the old memories would still exist in the brain but would be less accessible than the new ones.

Despite such doubts, evidence for the theory of reconsolidation is piling up. One experiment, for example, has found that blocking the molecules involved in protein degradation, which is necessary to break down synapses, makes animals forget a memory after it’s been recalled. The finding suggests that reconsolidation–which couldn’t happen without the initial breakdown–is the only way to explain why such memories don’t normally vanish.

A more recent experiment, published late last year, begins to get at the purpose of reconsolidation: it may help update memories, integrating them with information about related newer experiences. Jonathan Lee, a neuroscientist at the University of Birmingham in the United Kingdom, trained rats to fear a certain chamber by shocking them soon after they entered it. More training strengthened the association; evoking the memory made these rats freeze for longer than rats trained over just one day. Then Lee blocked a protein required for the consolidation of new memories; in a second set of animals, he instead blocked a gene that is critical to reconsolidation. He found that blocking consolidation did not interfere with the strengthening of the memory, while blocking reconsolidation did. This suggests that reconsolidation, not consolidation, is what’s important in strengthening memories, which is one way of updating them. “Learning something for the second time seems to use the reconsolidation mechanism,” says Lee. “Learning is strengthened by going back to the initial memory.”

Lee’s work implies that new versions of a memory are not laid down on top of a surviving old version when the memory is updated, as Miller’s alternative explanation suggests. Rather, the instability of a recalled memory may be crucial to the updating process. “Our assumption is that when you activate a memory, you set it up to be updated,” says Lynn Nadel, a neuroscientist at the University of Arizona. “You make [the memory] fragile so that it is open to being changed.”

Still, many questions about reconsolidation remain. Several experiments have shown that under some circumstances, erased memories can come back, suggesting that the initial memory was not truly erased. Meanwhile, both the age of the memory and its initial strength sometimes seem to affect how malleable it is: older memories, for example, can be more resistant to alteration, though that’s not always the case. Some scientists see these limitations as evidence that Nader’s theory of reconsolidation doesn’t adequately explain recall-induced forgetting. But it may be that reconsolidation happens only under specific conditions or with specific types of memory, while other mechanisms are used to update memory in the other situations. What we don’t yet understand is which types of memory are vulnerable to alteration and under what circumstances, says Jerry Rudy, a neuroscientist at the University of Colorado in Boulder, the author of The Neurobiology of Learning and Memory. Other researchers are now exploring whether reconsolidation is a fairly limited occurrence or one that’s fundamental to memory as we conceive of it.

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Credits: Gérard dubois, Bryan Christie Design
Video by Emily Singer

Tagged: Biomedicine

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