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Drs. Calin-Jageman Discover Molecular Fragments of Memory in Sea Slugs

Thursday, February 8, 2018

Drs. Bob and Irina Calin-Jageman are celebrating the 10th anniversary of Dominican University’s neuroscience lab with an exciting breakthrough in their ongoing research on memory and forgetting. They believe they have uncovered the molecular fragments of forgotten memories in Aplysia californica, commonly known as the sea slug. A paper on their work has been published in the January issue of the science journal, Learning & Memory, and WTTW's Chicago Tonight recently covered their breakthrough.

“We’re fairly confident that this is the first work to show that genetic changes evoked by learning can outlast recall,” said Bob Calin-Jageman, professor of psychology and director of Dominican’s neuroscience program. “Our research indicates that even as memories fade, some molecular fragments of the memory can persist in the brain, where they might kickstart relearning. We’re excited that this work might open up new avenues to understanding the neuroscience of forgetting.”

The Calin-Jagemans have been doing painstaking research over the past decade, and have published two papers focusing on how the sea slugs remember—but this is the first paper they have produced that focuses specifically on what happens when the sea slug forgets. Their research, which has been ably assisted by students Leticia Perez, Ushma Patel and Marissa Rivota, has been supported by a three-year $300,000 grant from the National Institute of Mental Health.

During their experiments, the Calin-Jagemans subject the sea slugs to uncomfortable shocks on one side of their bodies—which instills a fear memory in the animal such that, thereafter, every time the animal is touched even slightly on the trained side, it reacts dramatically by curling into a ball. However, if the sea slug is left alone for several days, the memory seems to wear off—they seem to have forgotten the painful experience and, when touched again, their reaction isn’t nearly as dramatic. There is no longer evidence that the painful experience has changed the way they behave.

Even though the memory seems forgotten, the sea slugs can relearn very quickly. The Calin-Jagemans found that, once the slugs had forgotten the previously painful experience, just a brief shock caused the dramatic response to return. Most species, including humans, display easier relearning for what seems to be forgotten memories. This relearning indicates that some fragment of the memory is still present in some fashion. The puzzling question is, what is this fragment?

To discover the answer to this question, the Calin-Jagemans first had to determine what is going on in the sea slug’s brain before any forgetting occurs. They profiled over 30,000 direct Aplysia genes and found that over 1,200 were still activated one day after the shocks were applied to the animal, when the memory of the shocks was still fresh. When they profiled the same genes one week later, the vast majority of the genes were switched off. However, they were thrilled to find that 11 of the original genes remained active—perhaps representing that lingering fragment of memory that could help with relearning.

According to Irina Calin-Jageman, professor of biology, this is the most exciting finding of her career. “To see that there is a nugget left in the brain that could represent a mostly forgotten memory is just astonishing. This is evidence that the brain holds weak physical traces of previous experiences; that the brain is reconfigured in a way that is different than before,” she said.

The next step in their research is to figure out what these activated genes are doing, why they are still there and how they might help bring the memory back. “What we need to do next is disrupt these genes and see if that makes it harder or easier to relearn memory. But that will take more time and more funding,” Bob Calin-Jageman said.

While the Calin-Jagemans can’t predict how applicable their findings might be to the human brain, they hope that their work will give other researchers a foothold for exploring forgetting and recovery in their more complex research animals. They acknowledge that the evolutionary connection between the sea slug and humans is very distant—but their work represents a good start.

“Forgetting is something we really don’t understand. Most of the scientific research has been on how information gets into the brain, not how it fades. If we can better understand forgetting, perhaps we can discover breakthrough pharmaceuticals or methods to help slow down the process,” Irina Calin-Jageman said.

As excited as the Calin-Jagemans are about the potential of this findings, they’re pretty sure it won’t help people remember where they left their keys. And they assert that there are some memories people just might want to permanently forget—like that awkward junior prom date…

Why the sea slug?

The benign (but beloved) sea slugs have been perfect partners for the Calin-Jagemans’ research because they have such rudimentary nervous systems, containing only 10,000 neurons compared to the 80 billion neurons typical in humans. Even honeybees have a million neurons and ants have 100,000. Because the sea slugs have so few neurons, each neuron is easy to find and isolate. In addition, the sea slugs are fairly large and docile.

Trying to find the genes in the human brain responsible for memory would be like trying to find a needle in a haystack. And any changes in the human brain chemistry would be infinitesimal. But, with the sea slug, the Calin-Jagemans know exactly which neurons store memory and can manipulate only those neurons.