How the brain forgets

01 February 2019
By Evan Wroe.

MEMORY-FILES

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Researchers have uncovered a way to block the process of forgetting, delving deeper into the mechanisms that make memories fade...

According to a new study, the process by which memories are forgotten relies upon specific machinery in the brain's nerve cells. But if this process is blocked by adding a small, tailor-made molecule, it's possible to prevent memories from fading away.

Memory and learning are important parts of all of our lives, particularly with respect to conditions like post-traumatic stress disorder (PTSD) and Alzheimer’s. And while the ability to retain memories may sound appealing, forgetting is a useful skill in itself. Indeed, some argue that the ability to forget is key to our survival and success as a species, because it allows us to learn from mistakes and adapt to new environments.

Writing in the journal Science, Ankit Awasthi and his team at the European Neuroscience Institute, in Göttingen, Germany identified a protein called Syt3 as a key linchpin in memory-making. To investigate its role, the researchers compared normal mice with animals termed "Syt3-knockouts" that had been genetically modified not to produce any Syt3. The team tested the abilities of the mice to learn and forget using a series of mazes.

In one test, the mice learned their way to a certain point in the maze to retrieve a food reward. Both the normal and the Syt3-knockout mice were able to do this equivalently well. But when the food was moved to a new position in the maze, while the unmodified mice rapidly learnt the new food location and forgot about the first food location, the Syt3 knockout mice consistently visited the original location first, before moving on to the new location. This, the researchers suggest, indicates that the knockout animals were unable to forget the original food location.

Interestingly, the small molecule that the researchers developed to block Syt3 was able to replicate the effect of the knockout; injected into the brains of normal mice, it prevented them from forgetting too.

In the brain, memories are stored as molecular and cellular changes within synapses, the connections between neurones. One of the structures responsible for making memories is the AMPA receptor, a protein found at synapses that helps to pass signals from one neuron to another. The more this AMPA receptor is used, the more of it is made, so a memory is reinforced.

The purpose of Syt3, the membrane protein identified by Awasthi, is to recycle redundant AMPA receptors; this has the effect of weakening memory pathways that are not being used. So blocking Syt3 prevents AMPA receptor recycling, and the pathway cannot weaken, meaning memories won’t fade.

While the mechanisms for creating memories were previously quite well studied, until now the way in which memories are lost has received much less attention. The discovery of Syt3 as a principal player in the pathway of memory loss, and the demonstration of how this pathway could be used to tinker with the machinery of memory, means researchers are now in a much better position to understand and combat memory-based illnesses and to reveal more fully how our brains are operating at a molecular level.

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