An MIT study of the neural circuits that underlie memory process reveals, for the first time, that memories are formed simultaneously in the hippocampus and the long-term storage location in the brain’s cortex. This image shows memory engram cells (green and red) which are crucial for permanent memory storage in the prefrontal cortex. Credit: Takashi Kitamura
The brain’s process of storing short-term memories and then transferring them to another part of the brain for longer-term storage is now better understood.
Massachusetts Institute of Technology (MIT) researchers have studied the neural circuits that underlie this process and revealed for the first time that memories are actually formed simultaneously in the hippocampus and the long-term storage location in the brain’s cortex.
However, the long-term memories remain “silent” for about two weeks before reaching a mature state.
“This and other findings in this paper provide a comprehensive circuit mechanism for consolidation of memory,” Susumu Tonegawa, Ph.D., the Picower Professor of Biology and Neuroscience, the director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory and the study’s senior author, said in a statement.
The findings could lead to a revision of the dominant models of how memory consolidation occurs.
Studies dating back to the 1950’s have suggested that long-term episodic memories are stored outside the hippocampus, and scientists believe these memories are stored in the neocortex, the area of the brain also responsible for cognitive functions including attention and planning.
There are two major models to describe how memories are transferred from short-to-long-term memory. The standard model proposes that short-term memories are initially formed and stored in the hippocampus only, before being gradually transferred to long-term storage in the neocortex and disappearing from the hippocampus.
The more recent model—the multiple trace model—suggests that traces of episodic memories remain in the hippocampus and store details of the memory, while the more general outlines are stored in the neocortex.
However, until recently scientists were unable to truly test these theories. Most previous studies of memory were based on analyzing how damage to certain brain areas impacts memories, but in 2012 Tonegwawa’s lab developed a way to label engram cells, which contain specific memories.
This enabled the researchers to trace the circuits involved in memory storage and retrieval. They can also artificially reactive memories by using optogenetics—a technique that allows them to turn target cells on or off using light.
Using mouse models, researchers used this technique to label memory cells in ice during a fear-conditioning event—a mild electric shock delivered when the mouse is in a particular chamber. They then use light to artificially reactive these memory cells at different times and see if that reactivation provoked a behavioral response from the mice. This also helped them 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 memory cells were labeled in the hippocampus, the prefrontal cortex and the basolateral amygdala, which stores memories’ emotional associations.
A day after the fear-conditioning event, the researchers discovered that memories of the event were being stored in engram cells in both the hippocampus and the prefrontal cortex, but 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,” research scientist Takashi Kitamura said. “This is contrary to the standard theory of memory consolidation, which says that you gradually transfer the memories. The memory is already there.”
During 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 mice to naturally recall the event.
However, by the end of the two-week period, the hippocampal engram cells became silent and were no longer needed for natural recall, while traces of the memory remained and reactivated those cells with light.
In the basolateral amygdala, once memories were formed, the engram cells remained unchanged throughout the course of the experiment and 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.
The next step for the research team is to conduct further studies to determine whether memories fade completely from hippocampal cells or if some traces remain. They also plan to further investigate how the prefrontal cortex engram maturation process occurs.
