Can Lost Memories Be Restored in Alzheimer’s Patients?

A recent study published in the journal eLife suggests that it might be possible to restore lost memories.

Over the past century, evidence suggested that long-term memories are expressed in the brain by changes in synaptic connections, which are destroyed in neurodegenerative disorders. However, in a recent news release, Dr. David Glanzman, senior author of the study, and professor of integrative biology and physiology and of neurobiology at UCLA said “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. If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible.”

In their study entitled ”Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia,” a team of researchers from the University of California, Los Angeles (UCLA), using marine snails called Aplysia californica, examined if long term memory (LTM) is stored in the synapses by analyzing the snails’ learning and memory processes.

The Aplysia is known to express a defensive response to protect its gill from potential harm (withdrawal reflex), however, the sensory and motor neurons that produce this withdrawal effect are unknown.

The researchers enhanced the animal’s withdrawal reflex by giving electric shocks that caused the release of serotonin in the snail’s central nervous system. Long-term memory occurs due to the growth of new synaptic connections caused by serotonin, as Glanzman explained. When LTMs are being formed, the brain is constantly creating new proteins to produce new synapses. However, in neurodegenerative disorders this process is disrupted, the proteins are not synthesized and LTM are not formed.

“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 in the news release. “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 of researchers studied the sensory and motor neurons mediating the snail withdrawal reflex in a Petri dish and found that the neurons were able to regenerate synaptic connections that existed when the neurons were in their natural state. Then they added serotonin and observed new synaptic connections being formed between the sensory and motor neurons. However, if they added serotonin straightaway followed by the addition of a substance that inhibits protein synthesis, the new synaptic growth was prevented, and LTM was not formed.

To understand if the new synapses disappeared when memories were lost, the researchers counted the synapses and recounted them after 24 hours and after they added an inhibitor of the protein synthesis. Results showed that the synapses’ connectivity was enhanced, with the protein synthesis inhibitor not affecting LTM.

Moreover, the researchers replicated the experiment with the serotonin that functioned as a reminder to the neurons of the original training. They added the serotonin to a Petri dish with sensory and motor neurons, and after 24 hours, the results revealed that the synaptic growth and LTM were erased, suggesting that the serotonin triggers a new round of memory consolidation, and that inhibiting protein synthesis during this “reconsolidating” deleted the memory in the neurons.

“That suggests that the memory is not in the synapses but somewhere else,” Glanzman said. “We think it’s in the nucleus of the neurons. We haven’t proved that, though.”

“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,” he said.

Findings from this study strongly alter common knowledge regarding stable synapses storage of long-term memories.