Researchers may be able to restore lost memories in early-stage Alzheimer’s patients, suggests a new study which found that long-term memories may not be stored in synapses as previously thought.
Most neuroscientists have believed that memories are stored at the synapses – the connections between brain cells, or neurons – which are destroyed by Alzheimer’s disease.
“Long-term memory is not stored at the synapse. That’s a radical idea, but that’s where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections,” said David Glanzman, senior author of the study, and a University of California – Los Angeles professor.
“If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible,” he said. Glanzman’s research team studied a type of marine snail called Aplysia. They enhanced the snail’s withdrawal reflex by giving it several mild electrical shocks on its tail.
The shock causes the hormone serotonin to be released in the snail’s central nervous system. Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, said Glanzman.
As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted the proteins may not be synthesised and long-term memories cannot form.
In an experiment, researchers placed sensory and motor neurons that mediate the snail’s withdrawal reflex in a Petri dish, where the neurons re-formed the synaptic connections that existed when the neurons were inside the snail’s body.
When serotonin was added to the dish, new synaptic connections formed between the sensory and motor neurons.
But if the addition of serotonin was immediately followed by the addition of a substance that inhibits protein synthesis, the new synaptic growth was blocked; long-term memory could not be formed.
Researchers wanted to understand whether synapses disappeared when memories did. They counted synapses in the dish and 24 hours later added a protein synthesis inhibitor.
They found new synapses had grown and synaptic connections between neurons had been strengthened.
Next, the scientists added serotonin to a Petri dish containing a sensory neuron and motor neuron, waited 24 hours, and then added another brief pulse of serotonin – which served to remind the neurons of the original training – and immediately afterward added the protein synthesis inhibitor.
They found that synaptic growth and memory were erased. When they re-counted the synapses, they found that the number had reset to the number before the training, Glanzman said.
If memories are stored in the synapses the researchers should have found that the lost synapses were the same ones that had grown in response to the serotonin. Instead, they found that some of the new synapses were still present and some were gone, and some of the original ones were also gone.
Glanzman said there was no obvious pattern to which synapses stayed and which disappeared, which implied that memory is not stored in synapses.