Lisman lab discovers key to long-term memory, furthering research on Alzheimer’s and addiction

October 13, 2017

Since the 1980’s, Professor John Lisman ’66 (BIOL) has investigated the relationship between memory and calcium/calmodulin dependent protein kinase (CaMKII). On Sept. 27, Lisman’s Lab’s breakthrough study demonstrating that CaMKII stores long-term memories was published in the online edition of “Neuron,” a peer-reviewed neuroscience journal.

The discovery, achieved through experimentation on rats by the lab of John Lisman, who is also the Zalman Abraham Kekst Chair in Neuroscience, is a testament to research at Brandeis, as the first seven authors of the paper are Brandeis undergraduates. The neuron paper was coauthored by Tom Rossetti ’18, Somdeb Banerjee ’20, Chris Kim ’19, Megan Leubner ’18, Casey Lamar ’18, Pooja Gupta ’16, Bomsol Lee ’15, Rachael Neve (of Massachusetts General Hospital) and Lisman.

“That kind of structure isn’t something that you would get at… many universities… It’s the combination of the amount of trust that…the lead investigators [and] that doctor Lisman has in his students. But also it’s a testament to the type of support that Brandeis is giving, [and] the type of opportunities that Brandeis is giving,” said Lamar, who worked on the study.

By demonstrating the link between memory and CaMKII, the study holds possible answers to topics that have baffled neuroscientists for ages, such as Alzheimer’s disease, dementia and addiction.

CaMKII has been linked with Alzheimer’s disease in the past, and a further understanding of the enzyme could help understand how the disease affects memory. In theory, the results could also be used to edit memories and unlearn the associations that addicts have with their addiction.

According to Lamar, Lisman and his team were a model of perseverance. “For him, for a lot of these scientists it’s more about [how] they’re never satisfied… They’re never satisfied with the answers they have. They’re never satisfied with the explanations that… other people have given… Its more about…trying to search out every answer for themselves.”

Lisman himself did not give up, despite when, in 2009, a study from SUNY Downstate Medical Center showed that another kinase enzyme was key to memory storage (though later studies soon cast doubt on those findings). Even the day after publishing the study, the team assembled for another meeting to explore how calmodulin, the protein that binds to CaM-kinase, might be affected by other inhibitors.

CaMKII helps maintain a process that strengthens synapses, which are the connections between neurons that allow them to communicate with each other. A memory is essentially the path—from neuron to synapse to neuron—that an electrochemical signal follows. The more that pathway is strengthened, the more likely the memory is to become a long-term memory.

The experiment was conducted using rats as test subjects. The rats were placed on a rotating platform with a shock zone that was marked by visual cues on the wall adjacent to the platform, and the rats learned to avoid the shock zone.

After the learning period, the rats were injected with a Herpes simplex virus, which stopped CaMKII from working in the rodents’ brain when expressed. When they placed the rats back on the platform, the researchers found that the rats no longer avoided the shock zone. The memory of the shock zone had been erased.

To confirm that it was the memory that had been erased, not the ability to have or make memories, the researchers tested the rats again and showed that they could form new memories.

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