Researchers have labelled memory cells in mice during a fear-conditioning event — that is, a mild electric shock delivered when the mouse is in a particular chamber. Then, they could use light to artificially reactivate these memory cells at different times and see if that reactivation provoked a behavioral response from the mice (freezing in place). The researchers could also determine which memory cells were active when the mice were placed in the chamber where the fear conditioning occurred, prompting them to naturally recall the memory.
The researchers labeled memory cells in three parts of the brain:
the prefrontal cortex, and
the basolateral amygdala, which stores memories’ emotional associations.
Just one day after the fear-conditioning event, the researchers found that memories of the event were being stored in engram cells in both the hippocampus and the prefrontal cortex. However, the engram cells in the prefrontal cortex were “silent” — they could stimulate freezing behavior when artificially activated by light, but they did not fire during natural memory recall.
“Already the prefrontal cortex contained the specific memory information,” Kitamura says. “This is contrary to the standard theory of memory consolidation, which says that you gradually transfer the memories. The memory is already there.”
Over the next two weeks, the silent memory cells in the prefrontal cortex gradually matured, as reflected by changes in their anatomy and physiological activity, until the cells became necessary for the animals to naturally recall the event. By the end of the same period, the hippocampal engram cells became silent and were no longer needed for natural recall. However, traces of the memory remained: Reactivating those cells with light still prompted the animals to freeze.
In the basolateral amygdala, once memories were formed, the engram cells remained unchanged throughout the course of the experiment. Those cells, which are necessary to evoke the emotions linked with particular memories, communicate with engram cells in both the hippocampus and the prefrontal cortex.
“This paper shows clearly that from the get-go, engrams are formed in the prefrontal cortex,” says Paul Frankland, a principal investigator in the Neurobiology Laboratory at the Hospital for Sick Children in Toronto, who was not involved in the study. “It challenges the notion that there’s a movement of the memory trace from the hippocampus to the cortex, and makes the point that these circuits are engaged together at the same time. As the memories age, there’s a shift in the balance of which circuit is engaged as a memory is recalled.”
Further studies are needed to determine whether memories fade completely from hippocampal cells or if some traces remain. Right now, the researchers can only monitor engram cells for about two weeks, but they are working on adapting their technology to work for a longer period.