3rd July 2017

Select memories can be erased, leaving others intact

A study of snail neurons, published in Current Biology, suggests memories that trigger anxiety and PTSD could be "erased" without affecting normal memory of past events.

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. Published in Current Biology, the findings suggest that it may be possible to develop drugs to "delete" memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.

During their experiments, researchers stimulated two sensory neurons connected to a single motor neuron of the snail; 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, it was 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 these two 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 their results could be useful in understanding human memory, because vertebrates have similar versions of the snail proteins that create long-term memories. The PKM-protecting protein KIBRA is also 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 co-author Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC. "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 maintenance of non-associative memory."

Future studies in preclinical models are needed, the researchers say, to better understand how PKMs are produced and localised at the synapse before it can be determined which drugs may weaken non-associative memories.

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