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How the brain keeps track of similar but distinct memories

a subsection of the hippocampus

Salk researchers discovered how the brain keeps track of similar but distinct memories. This microscope image shows neural activity in the dentate gyrus, a subsection of the hippocampus where distinct groups of cells were active during the learning episodes (green) and memory retrieval (red).

The process of tak ing complex memories and converting them into representations that are less easily confused is known as pattern separation. Computational models of brain function suggest that the dentate gyrus, a subregion of the hippocampus, helps us perform pattern separation of memories by activating different groups of neurons when an animal is in different environments. Previous laboratory studies, however, found that the same populations of neurons in the dentate gyrus are active in different environments and that the cells distinguished new surroundings by changing the rate at which they sent electrical impulses—a discrepancy that perplexed neuroscientists.

A team of scientists led by Fred H. Gage has now discovered how the dentate gyrus helps keep memories of similar events and environments separate.

"Every day, we have to remember subtle differences between how things are today versus how they were yesterday—from where we parked our car to where we left our cellphone," explains Gage. "We found how the brain makes these distinctions, by storing separate 'recordings' of each environment in the dentate gyrus."

Gage's team compared the functioning of the mouse dentate gyrus and another region of the hippocampus, known as CA1, using laboratory techniques for tracking the activity of neurons at multiple time points. What they found was that the dentate gyrus and CA1 subregions functioned differently. In CA1, the same neurons were active during the learning and retrieval of memories. In the dentate gyrus, however, distinct groups of cells were active during learning episodes and retrieval, and exposing the mice to two subtly different environments activated two distinct groups of cells in the dentate gyrus.

"This finding supported the predictions of theoretical models that different groups of cells are activated during exposure to similar, but distinct, environments," says postdoctoral researcher Wei Deng. "This contrasts with the findings of previous laboratory studies, possibly because they looked at different subpopulations of neurons in the dentate gyrus."

In clarifying how the brain stores and distinguishes between memories, the discovery, reported in eLife, may also help identify how neurodegenerative diseases such as Alzheimer's rob people of these abilities.