A specific sequence of neurons must fire at just the right time to remember a particular event. For this to happen, neurons must be connected in a certain way by chemical junctions called synapses, reports New Scientist.
However, how they last over decades, given that proteins in the brain, including those that form synapses, are destroyed and replaced constantly, remains a mystery.
Now, Courtney Miller and David Sweatt, from the University of Alabama in Birmingham, say that a process called DNA methylation - the addition of chemical caps called methyl groups onto our DNA - may be responsible for preserving long-term memories.
Many genes are already coated with methyl groups. When a cell divides, this "cellular memory" is passed on and tells the new cell what type it is - a kidney cell, for example.
The researchers argue that in neurons, methyl groups also help to control the exact pattern of protein expression needed to maintain the synapses that make up memories.
They started the study by examining short-term memories. When caged mice are given a small electric shock, they normally freeze in fear when returned to the cage.
However, then injecting them with a drug to inhibit methylation seemed to erase any memory of the shock.
The researchers also showed that in untreated mice, gene methylation changed rapidly in the hippocampus region of the brain for an hour following the shock.
However, a day later, it had returned to normal, suggesting that methylation was involved in creating short-term memories in the hippocampus.
In order to see whether methylation plays a part in the formation of long-term memories, the researchers repeated the experiment, this time looking at the uppermost layers of the brain, called the cortex.
They found that a day after the shock, methyl groups were being removed from a gene called calcineurin and added to another gene.
Because the exact pattern of methylation eventually stabilised and then stayed constant for seven days, when the experiment ended, the researchers say the methyl changes may be anchoring the memory of the shock into long-term memory, not just controlling a process involved in memory formation.
"We think we're seeing short-term memories forming in the hippocampus and slowly turning into long-term memories in the cortex," said Miller.
The results were presented at the Society for Neuroscience meeting in Washington DC.