Two Aplysia sensory neurons with synaptic contacts on the same motor neuron in culture after isolation from the nervous system of Aplysia. The motor neuron has been injected with a fluorescent molecule that blocks the activity of a specific Protein Kinase M molecule. Credit: Schacher Lab/Columbia University Medical Center.
Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University and published today in Current Biology.
The new study tested that hypothesis by stimulating two sensory neurons connected to a single motor neuron of the marine snail Aplysia; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory.
By measuring the strength of each connection, the researchers found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased — without affecting the other — by blocking one of the PKM molecules.
In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.
The researchers say that their results could be useful in understanding human memory because vertebrates have similar versions of the Aplysia PKM proteins that participate in the formation of long-term memories. In addition, the PKM-protecting protein KIBRA is expressed in humans, and mutations of this gene produce intellectual disability.
“Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response,” says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. “By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient’s normal memory of past events.”
“Our study is a ‘proof of principle’ that presents an opportunity for developing strategies and perhaps therapies to address anxiety,” said Dr. Schacher. “For example, because memories are still likely to change immediately after recollection, a therapist may help to ‘rewrite’ a non-associative memory by administering a drug that inhibits the maintenance of non-associative memory.”
Future studies in preclinical models are needed to better understand how PKMs are produced and localized at the synapse before researchers can determine which drugs may weaken non-associative memories.