ITHACA, N.Y. – Manipulating mouse brains during sleep improved their ability to remember new experiences that would normally be forgotten – a finding with important implications for treating Alzheimer's disease and other forms of dementia that act on similar processes.
The study published in Neuron, is relevant to humans as the basic mechanisms of memory formation are very similar across mammals.
By selectively manipulating brain activity at specific times during sleep, the scientists found the mice remembered new experiences that were otherwise too brief for them to retain.
The researchers identified large sharp-wave ripples, a subset of brain activity patterns around 100 milliseconds long that is involved in consolidating and transferring new experiences from the hippocampus to the neocortex, where they are more permanently stored. The large sharp-wave ripples can now help researchers identify when new experiences are being converted to long-term memory.
"This study advance our understanding of memory processing in the brain," said Azahara Oliva , assistant professor of neurobiology and behavior. Oliva is a senior author of the study along with assistant professor Antonio Fernandez-Ruiz .
In the study, Fernandez-Ruiz and Oliva recorded neuron activity in the hippocampus and neocortex. They identified large sharp-wave ripples in the hippocampus, which occur during sleep, and are then propagated to the neocortex.
"Ripples are mediating the transfer of memory from the initial encoding in the hippocampus to long-term stable storage in the neocortex," Fernandez-Ruiz said.
The researchers observed that when an animal doesn't remember an experience, large sharp-wave ripples were weak during sleep, but when it does remember, there were many of these ripple events.
Once the researchers identified this pattern, they used an advanced technique called optogenetics to shine a light in the brain with an optic fiber that then selectively activated neurons. Optogenetics allowed the team to stimulate neurons at precise times to boost large sharp-wave ripples, which then consolidated a memory of an event the animal experienced right before sleep.
The team exposed mice to a new toy for five minutes and tested four hours later and found the animals didn't remember. They then boosted ripples associated with that experience during sleep, and they found the mouse then did remember the object. The technique even worked in mice engineered to have cognitive deficits.
"We were able to extend this memory consolidation in a condition where animals are unable to remeber without our help," Fernandez-Ruiz said.
This has important implications for better understanding Alzheimer's disease, as these memory consolidation processes are also impaired in humans. In next steps, the researchers will apply the same manipulations in mice engineered to exhibit conditions similar to Alzheimer's disease.
