In a previous column, I wrote about a star of the neuroscience research lab, a species of sea snail known as Aplysia californica. This little mollusk has contributed a lot to our understanding of learning and memory.

In 2012, Jack Byrne, who is director of the W.M. Keck Center for the Neurobiology of Learning and Memory at the University of Texas Health Medical School, reported that he and his team had used the sea snail to test the most effective time sequence for learning. "Snails are like all animals in that they learn better when training sessions are spaced over time rather than massed together. But given that spaced training is better, the question arises as to what is the optimal spacing…" Byrne said.

For that research, Byrne and his colleagues gave two groups of snails five learning sessions. One group trained in regular 20-minute intervals. The other received learning sessions at irregular intervals as predicted by a mathematical model. The model built on earlier research that identified proteins linked to memory; it predicted when the activity of the proteins might be aligned for the best learning experience.

Five days after the learning sessions were completed, a significant increase in memory was detected in the group that was trained with a schedule predicted by a computer. But no increase was detected in the group with the regular 20-minute intervals. To confirm their findings, researchers analyzed nerve cells in the brain of snails and found greater activity in the ones receiving the enhanced training schedule. The study revealed that memory could be enhanced appreciably with the right schedule of training.

“The logical follow-up question was whether you could use the same strategy to overcome a deficit in memory,” Byrne said. “Memory is due to a change in the strength of the connections among neurons. In many diseases associated with memory deficits, the change is blocked.”

UT researchers Yili Zhang, Jack Byrne, and Rong-Yu Liu.

Now, in a new proof-of-principle study published in the April 17 issue of The Journal of Neuroscience, Byrne's team reports reversing memory loss in the nerve cells of sea snails by determining when the cells were primed for learning. The scientists used optimized training schedules to retrain the cells, thus helping them compensate for memory loss.

For this new experiment, the research team blocked the activity of a gene that produces a memory protein in the sensory cells of sea snails. In so doing, they simulated a brain disorder in a cell culture. With the protein blocked, the strength of the connections among neurons responsible for long-term memory was diminished. To mimic training sessions, cells were administered a chemical at intervals prescribed by the mathematical model. After five training sessions administered at irregular intervals, the strength of the connections returned to near normal in the impaired cells.

“Although much works remains to be done, we have demonstrated the feasibility of our new strategy to help overcome memory deficits,” said Byrne. Byrne hopes his procedures can someday help individuals with cognitive deficits associated with brain disorders. "However, to apply the strategy to humans, it will first be necessary to learn more about memory circuits in the brain and the biochemical reaction steps within those circuits." Nonetheless, this kind of basic research lays the groundwork for numerous future applications, including the treatment of Alzheimer's.

For More Information:

Yili Zhang, Rong-Yu Liu, George A. Heberton, Paul Smolen, Douglas A. Baxter, Leonard J. Cleary, and John H. Byrne. Computational design of enhanced learning protocols. Nature Neuroscience. Published online Dec. 25, 2011.

Rong-Yu Liu, Yili Zhang, Douglas A. Baxter, Paul Smolen, Leonard J. Cleary, and John H. Byrne. Deficit in long-Term synaptic plasticity is rescued by a computationally predicted stimulus protocol. Journal of Neuroscience. Published online April 17, 2013.

Photo Credit:

Sea slug photo taken by by Daniel Geiger, the Sea Slug Forum 

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