How the brain is able to store memories over long periods of time has been a persistent mystery to scientists. In a new study in rats, a research team at the University of Oslo in Norway demonstrates that long-lived extracellular matrix molecules called perineuronal nets are essential for the recall of remote, but not recent, visual fear memories; and that removal of the nets disrupts remote memories.
This image shows a perineuronal net (green) surrounding a neuron. Image credit: Kristian Lensjø.
“Perineuronal nets are made up of sugar-coated proteins, forming a rigid structure that contains holes where connections to other neurons are kept in place,” said study senior author Dr. Marianne Fyhn and colleagues.
“When new memories are formed, the connections between neurons change.”
The researchers hypothesized that perineuronal nets might stabilize the new, memory-related connections to support long-term memories.
To test memory function, they performed a classical conditioning experiment, where rats learn to associate a light blink with an unpleasant event. This type of learning creates a robust and long-lasting memory.
“After learning, the rats were divided into two groups, one where the perineuronal nets were left intact and one where they were removed in a small area of the cortex, termed secondary visual cortex, an area known to be involved in memory storage,” they explained.
“When the rats were ‘asked’ to recall the memory a month later, the results were astonishing — the group without the nets did not remember anything.”
The experiments show that perineuronal nets are essential for long-term memories, because without them, the memory is lost.
“We were quite surprised by how strong the effect was in those first experiments, since we only manipulated molecules outside the neurons and not inside,” said co-author Dr. Elise Thompson.
“While we expected to see some effect of the intervention, previous studies on the nets had focused on their role in development and learning, not memory storage. It was very exciting to see that the memory was in fact gone.”
In a follow-up experiment where the memory was tested only a few days after learning, the scientists found that the memory was intact, and that the disappearing effect was specific to old memories.
“Because the net is a very stable structure it may stabilize memories as they age, but when a memory is new, it survives without extra stabilizing factors,” said co-author Dr. Kristian Lensjø.
This research is an important step toward understanding what components are needed to store memories for a lifetime.
“If we can increase our understanding of how memories are processed over months and years in the healthy brain, we can start to untangle what goes wrong when they are eventually lost in detrimental diseases like Alzheimer’s and dementia,” Dr. Fyhn said.
“The surprising finding that extracellular molecules are involved in these processes also suggests potential novel drug targets.”
The findings are published in the Proceedings of the National Academy of Sciences.
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Elise Holter Thompson et al. Removal of perineuronal nets disrupts recall of a remote fear memory. PNAS, published online December 26, 2017; doi: 10.1073/pnas.1713530115
