Episodic memories are about specific places and events. Kazumasa Tanaka, Brian Wiltgen and colleagues from University of California Davis applied a novel technique called optogenetics to test a long-standing idea about memory retrieval.

For about 40 years, neuroscientists have theorised that retrieving episodic memories involves coordinated activity between the cerebral cortex and the hippocampus, a small structure deep in the brain.

"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. If the hippocampus is damaged, patients can lose decades of memories," Tanaka explained.

The team used genetically-modified mice so that when nerve cells are activated, they both fluoresce green and express a protein that allows the cells to be switched off by light.

They were able both to follow exactly which nerve cells in the cortex and hippocampus were activated in learning and memory retrieval, and switch them off with light directed through a fibre-optic cable.

Tanaka and Wiltgen first showed that they could label the cells involved in learning and demonstrate that they were reactivated during memory recall.

"We were able to switch off the specific nerve cells in the hippocampus and show that the mice lost their memories of the unpleasant event," Tanaka said.

They were also able to show that turning off other cells in the hippocampus did not affect retrieval of that memory, and to follow fibres from the hippocampus to specific cells in the cortex.

"The cortex cannot do it alone. It needs input from the hippocampus. This has been a fundamental assumption in our field for a long time and the data provides the first direct evidence that it is true," Wiltgen noted.

They could also see how the specific cells in the cortex were connected to the amygdala a structure in the brain that is involved in emotion and in generating the freezing response.

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