How Lasting Memories Form In The Brain

The cells responsible for long-term memories are formed the prefrontal cortex during the initial experience and gradually strengthen over time.

AsianScientist (Apr. 18, 2017) – Contrary to popular belief, the cells responsible for long-term memory are formed at the same time as the cells responsible for episodic memory. These findings have been published in Science.

Being able to remember experiences long after they have happened is a basic part of life that guides behavior and even helps form personalities. Episodic memories, which are known to be short-lived, are thought to begin in a region of the brain called the hippocampus. Long-term memories on the other hand are thought to form gradually over time as new engram cells in the cerebral cortex, the outer gray matter of the brain.

The present study led by Professor Susumu Tonegawa demonstrates that this theory is only partially correct.

“We discovered the existence of cortical engram cells, but it turns out that they are not formed gradually over time. They actually form at the same time as the initial memory in the hippocampus,” explained study lead author Dr. Takashi Kitamura.

Just as Pavlov famously conditioned his dog to salivate at the sound of a bell, the team used conditioning to study contextual memory in rats. To determine which areas in the cortex were important for forming the long-term memory, they used optogenetics to block inputs to different brain areas during conditioning or during memory recall over a three-week period and found that long-term recall was affected only when information transfer to the frontal cortex of the brain was blocked during conditioning.

“This was surprising,” noted Tonegawa, who is director of the RIKEN Brain Science Institute and the RIKEN-MIT Center for Neural Circuit Genetics, “because it indicated that the cortical memory was likely created on the very first day, and not gradually as has been assumed.”

Next, the team positively identified engram cells in the prefrontal cortex. To do so, they inserted light-sensitive ion channels into prefrontal cells that were active during conditioning, and then excited the cells with blue light when the animals were in an unconditioned context. As with their previous studies in the hippocampus, this caused the mice to exhibit behavior indicative of their remembered experience—a hallmark of engram cells.

By definition, animals should be able to remember an event when engram cells respond naturally to a conditioned context, and should be unable to do so when the cells are silent. The team showed that this was true for the cortical engram cells, but only when tested more than a week after conditioning, when the hippocampal engram cells had already lost their memories.

“Although the engram cells were formed on the first day, they could only be activated naturally much later. This means that it took time for them to mature and change from silent engrams to active ones,” Kitamura said.

Further testing showed that this maturation process required input over several days from the hippocampal engram cells. Inhibiting output from these cells after conditioning made it impossible to activate the frontal engram cells at later times. The team has also shown that engram cells for positive and negative emotional events form in another part of the brain called the amygdala, which is connected to both the hippocampus and the frontal cortex.

“Since the prefrontal cortex is also known to be crucial for rule learning and semantic memory formation, these results will allow researchers to delve deeper into the neural circuit mechanisms and engrams needed for their formation in the neocortex,” Kitamura added.

The article can be found at: Kitamura et al. (2017) Engrams and Circuits Crucial for Systems Consolidation of a Memory.


Source: RIKEN.
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