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Long-Term Memory Storage Begins Immediately

In mice, cells in the prefrontal cortex—where memories are maintained long-term—start to encode a fearful experience right from the start.

Jun 1, 2017
Kerry Grens

RECORDERS: Entorhinal cortex cells (red) that project to the prefrontal cortex are important for memory in mice.TAKASHI KITAMURA, TONEGAWA LAB

The paper
T. Kitamura et al., “Engrams and circuits crucial for systems consolidation of a memory,” Science, 356:73-78, 2017.

Memory theories
The theory goes that as memories form, they set up temporary shop in the hippocampus, a subcortical region buried deep in the brain, but over time find permanent storage in the cortex. The details of this process are sketchy, so Takashi Kitamura, a researcher in Susumu Tonegawa’s MIT lab, and colleagues wanted to pinpoint the time memories spend in each of these regions.

Total recall
As mice were subjected to a fearful experience, the team labeled so-called memory engram cells—neurons that are stimulated during the initial exposure and whose later activity drives recollection of the original stimulus (in this case, indicated by a freezing response). Using optogenetics, Kitamura turned off these cells in the prefrontal cortex (PFC) when the memory first formed as mice were exposed to a foot shock. Short-term memory was unaffected, but a couple of weeks later, the animals could not recall the event, indicating that PFC engrams formed contemporaneously with those in the hippocampus, not later, as some had suspected, and that this early memory trace in the cortex was critical for long-term retrieval.

Going dark
Over time, as untreated mice recalled the fearful event, engrams in the hippocampus became silent as PFC engrams became more active. “It’s a see-saw situation,” says Kitamura, “this maturation of prefrontal engrams and dematuration of hippocampal engrams.”

Circuit dynamics
Stephen Maren, who researches memory at Texas A&M University and was not part of the study, says the results reveal that the network circuitry involved in memory consolidation (of which Kitamura’s team dissected just one component) is much more dynamic than previously appreciated. “It’s the most sophisticated circuit-level analysis we have to date of these processes.”

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