Optogenetics Tests Memory Manipulation Theory

Optogenetics is giving scientists a better look at how different parts of the brain can work together to manipulate memories.

Using the light-based technique, researchers at the University of California, Davis, have been able to erase specific memories in mice. Their findings prove the basic theory of how different parts of the brain will work together to retrieve episodic memories, they said.

The researchers used mice genetically modified to make their nerve cells fluoresce green when activated by light and to make the cells express a protein that allows them to be switched off by light.

Activated cells in this mouse brain fluoresce green. The hippocampus helps the cells in the cortex recreate the pattern of activation from when the memory was formed, allowing the memory to be retrieved. Courtesy of Kazumasa Tanaka/Brian Wiltgen/University of California, Davis.

They trained the mice by placing them in a cage where they got a mild electric shock. Normally, mice placed in a new environment will nose around and explore. But when placed in a cage where they have previously received a shock, they freeze in place in a fear response.

The testing first showed that the researchers could label the nerve cells in the cortex and hippocampus that were activated in learning and memory retrieval, and then that they could also switch those memories off with light directed through a fiber optic cable. When they did this, the mice behaved in a normal way again, showing that they had lost their memories of the unpleasant event.

The investigators also demonstrated that turning off other cells in the hippocampus did not affect retrieval of those memories.

“The cortex can’t do it alone – it needs input from the hippocampus,” said Dr. Brian Wiltgen, an associate professor of psychology at UC Davis. “This has been a fundamental assumption in our field for a long time, and [this] data provides the first direct evidence that it is true.”

For decades, it has been theorized that retrieving such memories involves coordination of activity between the hippocampus and the cerebral cortex, according to the researchers.

“The theory is that learning involves processing in the cortex, and the hippocampus reproduces this pattern of activity during retrieval, allowing you to re-experience the event,” Wiltgen said, adding that if the hippocampus is damaged, patients can lose decades of memories.

Before optogenetics, this theory was difficult to test directly, the researchers said.

The work was funded by the Whitehall Foundation, the McKnight Foundation, the Nakajima Foundation and the National Science Foundation.

For more information, visit www.ucdavis.edu.