When the brain forms new short-term memories, it creates new neurons in a region of the hippocampus called the dentate gyrus. This process also clears outdated memories, making room for more new ones, say Joe Tsien of Princeton University, and his colleagues.
Patients with Alzheimer’s disease lose cells in the hippocampus, and one suggested treatment is to transplant stem cells into the region to replace the dead cells. But the new work suggests that the addition of new cells might in fact disrupt memory retention by dramatically altering connections between neurons in the hippocampus and boosting memory clearance, the researchers say.
“The dentate gyrus is very small and so it has very limited memory storage capacity, but it is the only part of the brain where adult neurogenesis occurs,” Tsien says.
“Although the addition of new neurons into the dentate gyrus represents a small fraction of the neural cells, their destabilising effect on existing neural connections can be amplified a thousand fold – affecting 30 per cent of neural connections in the hippocampus,” he told New Scientist.
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Memory overwrite
Richard Harvey, director of research at the Alzheimer’s Society, UK, says he is not surprised that stem cell transplants might damage memory. “Our view is that stem cells offer hope in disorders like Parkinson’s, but in Alzheimer’s the problem is more to do with the network connections of neurons,” he says. Transplanting new neurons could disrupt these networks, he says.
Tsien’s team bred mice with a mutation in the Presenilin 1 (PS1) gene, which they knew had a role in memory formation. The gene does not function properly in 90 per cent of patients with early onset Alzherimer’s disease.
The team tested the mice’s short-term memory by investigating whether they could remember the location of a wooden platform in a bowl of milk, for example. Surprisingly, the mice’s memory was unaffected. This shows that the creation of new neurons is not vital for memory formation.
Disneyland for mice
However, the team then investigated the mice’s ability to learn a variety of new tasks by placing them in a highly stimulating environment – a kind of “Disneyland for mice”, Tsien says. This kind of environment usually causes enhanced learning in mammals and increased generation of new neurons in the dentate gyrus.
But the researchers found that the modified mice formed fewer new memories than the controls. They also found that they formed no new neurons in the dentate gyrus. This implies that the formation of new neurons is vital for memory clearing.
The new research is very interesting, says John Cooper, a stem cell scientist at the Institute of Psychiatry in the UK. “For the first time we have a link between neurogenesis and memory clearance and the role PS1 plays,” he said. “Knowing anything about the memory mechanism is important progress in understanding Alzheimer’s disease.”
Journal reference: Neuron (vol 32, p 911)
