In this image of fluorescently labeled Aplysia neurons in cell culture, the green points, or puncta, represent sites of synaptic contact between the sensory (green) and motor (red) neurons.
New UCLA research indicates that lost memories can be restored, a finding that offers some hope for patients in the early stages of Alzheimer’s disease. The new study challenges the prevailing idea that memories are stored in 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,” says David Glanzman, PhD, 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.”
Dr. Glanzman’s research team studies a marine snail called Aplysia to understand the animal’s learning and memory. They are particularly interested in its withdrawal reflex and the sensory and motor neurons that produce it. By giving several mild shocks to the snail’s tail, releasing the hormone serotonin into the central nervous system, they enhanced its withdrawal reflex. The enhanced reflex lasted several days, indicating long-term memory.
Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, Dr. Glanzman says. As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted — for example by a concussion or other injury — the proteins may not be synthesized, and long-term memories cannot form.
Dr. Glanzman’s team found the same mechanism held true when studying the snail’s sensory and motor neurons in a Petri dish. 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 a substance that inhibits protein synthesis, the new synaptic growth was blocked; long-term memory could not be formed.
The scientists then examined what happens when serotonin was combined with sensory and motor neurons and followed 24 hours later with another pulse of serotonin — which acted as a “reminder” to trigger a new round of memory consolidation — and immediately afterward with the protein inhibitor; the synaptic growth indicating memory was erased.
If the prevailing wisdom were true — that 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. But that’s not what happened. Instead, they found that some of the new synapses were still present and some were gone, and that some of the original ones were gone, too. Dr. Glanzman says there was no obvious pattern to which synapses stayed and which disappeared, which implied that memory is not stored in synapses.
Dr. Glanzman believes the research could have significant implications for people with Alzheimer’s disease. “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 says.
"Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia," eLife, November 17, 2014.