New research suggests lost memories could potentially be restored in Alzheimer's patients, and a small snail species helped scientists prove it.
Scientists have long-believed memories are stored at the synapses (the connections between brain cells) which are broken down by Alzheimer's disease, but a new study suggests this is not necessarily true, UCLA reported.
"Long-term memory is not stored at the synapse," said David Glanzman, a senior author of the study, and a UCLA professor of integrative biology and physiology and of neurobiology. "That's a radical idea, but that's where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won't be easy, but I believe it's possible."
To make their findings the researchers looked at a marine snail called Aplysia and the sensory and motor neurons that help it produce a withdrawal reflex used to protect its gills. The team enhanced this withdrawal reflex by giving the snail several electric shocks on its tail and found the enhancement lasted for days, indicating the animal's long-term memory. The researchers believe the shock causes serotonin to be released into the snail's nervous system.
Long-term memory is believed to be a function of the growth of new synaptic connections brought about my serotonin. As these memories are formed the brain creates new proteins that lead to new synapses; a disruption of this process can prevent these memories from forming.
"If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn't remember the training," Glanzman said. "However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later. In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn't affect long-term memory. That's true in the Aplysia and in human's brains."
The team looked at the snail's neurons in a Petri dish, and found when serotonin was added to the sample, new synaptic connections were formed. When the researchers introduced a substance that inhibits protein synthesis, the new synaptic growth was blocked and long-term memory could not be formed.
The team also counted the number of synapses in a Petri dish and 24 hours later added a protein synthesis inhibitor. They found after an additional 24 hours new synapses had grown and synaptic connections had increased. In a following experiment they added serotonin containing a sensory neuron and motor neuron, adding an additional pulse of serotonin and the protein synthesis inhibitor after 24 hours. In this case the synaptic growth and memory were erased and the number of synapses had reset to where they were before training.
If memories are indeed stored in the synapses then researchers should have found lost synapses were the same ones that grew in response to serotonin, but instead they observed some were still present while some of the originals had disappeared. There was no observed pattern of which synapses stayed and which disappeared, suggesting memory is not stored in the synapses after all.
The researchers repeated the experiment and gave the snail a modest number of tail shocks, which did not produce long-term memories, and found the memories that were believed to be erased had returned. These findings suggest synaptic connections that are lost can potentially be restored.
"That suggests that the memory is not in the synapses but somewhere else. We think it's in the nucleus of the neurons. We haven't proved that, though." Glanzman said. "As long as the neurons are still alive, the memory will still be there, which means you may be able to recover some of the lost memories in the early stages of Alzheimer's."
The findings were published in a recent edition of the journal eLife.
