A new physiological mechanism for short-term memory storage in the brain

Whether it’s the pleasant experience of returning to one’s childhood home over the holidays or the unease of revisiting a site that proved unpleasant, we often find that when we return to a context where an episode first happened, specific and vivid memories can come flooding back. In a new study just published in leading journal Neuron, scientists report the discovery of a mechanism the brain may be employing to make that phenomenon occur.

The work was completed at Massachusetts Institute of Technology (MIT)’s Picower Institute for Learning and Memory, and involved Dr Tomás Ryan, who is now an Assistant Professor in Trinity College Dublin’s School of Biochemistry and Immunology and the Trinity College Institute of Neuroscience (TCIN).

Picower Professor of Neuroscience at MIT and senior author, Susumu Tonegawa (Nobel Laureate for Physiology or Medicine, 1987), said: “Suppose you are driving home in the evening and encounter a beautiful orange twilight in the sky, which reminds you of the great vacation you had a few summers ago at a Caribbean island. This initial recall could be a general recall of the vacation. But moments later, you may get reminded of details of some specific events or situations that took place during the vacation which you had not been thinking about.”

At the heart of that second stage of recall, where specific details are suddenly vividly available, is a change in the electrical excitability of engram cells or the specific ensemble of neurons that together encode a given memory, seemingly through their unique constellation of connections.

In the new study Professor Tonegawa’s lab, led by Dr Michele Pignatelli and Dr Tomás Ryan, showed that after mice formed a memory in a context, the engram cells encoding that memory in a brain region called the hippocampus would temporarily (for about 1 hour) become much more electrically excitable if the mice were placed back in the same context again. So, for instance, if they had a significant experience in a specific context one day, then the engram cells would be much more excitable for about an hour after they were put back in that same context the next day.

Image credit Nora Maria Raschle @bornascientist.

The specific change in the engram cells’ electrical properties has some direct implications for learning and behaviour that hadn’t been appreciated before.

Importantly, during that hour after returning to the initial context, because of the engrams’ elevated excitability, mice proved better able to distinguish between that context and distinct contexts even if they shared some similar cues. From an evolutionary perspective, the increase in excitability allows them both to learn to avoid places where danger happened very recently and to continue to function normally in places that happen to have some irrelevant resemblance. And because the effect is short-lived, it doesn’t oblige them to remain overly attuned for very long.

“The short-term reactivation increases the future recognition capability of specific cues,” Pignatelli and Tonegawa’s team wrote. “Engram cell excitability may be crucial for survival by facilitating rapid adaptive behaviour without permanently altering the fundamental nature of the long-term engram.”

Because these brain structures and behavioural functions are conserved across all mammals, it is clear that these discoveries can inform us of how short-term memory recall works in humans too.

Speaking about the study, Dr Tomás Ryan, added:

We were in a position to discover this previously unknown behavioural phenomenon – a new form of short-term memory – only because our hypothesis was based on the time period revealed by a physiological analysis of the specific engram cells that store the memory. This integrative story highlights the value and importance of studying the biology of engram cells directly, and how careful physiology analysis can lead to new psychological insights.

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