Manipulating Memories in the Brain

The first thing that comes to my mind when I hear people talk of memories is that they are speaking about something that presents itself as an image to their mind. An image retrieved from the recent to distant past. The image may be of me at about five years of age sitting on the California desert sand watching black ants busily running in and out of an entrance surrounded by a pile of sand miraculously extracted from the ground to make way for their tunnels. Introspection and research makes clear, however, that many types of memories exist including many that are not presented as images to the mind.

The creation of a false contextual memory in the dentate gyrus.
Figure 1. Labeled dentate gyrus neurons are the active neurons during learning and memory formation. Precisely which neurons are active depends on what is being remembered. The top left photo shows active neurons labeled red and then later an active set labeled green to the same learning and memory context. In the magnified view at top right you can see that many neurons are labeled with both red and green (yellow) indicating that the same neurons were activated each time. At lower left active neurons labeled red were presented with a different learning and memory context than those labeled green. In the magnified view at lower right a preponderance of neurons show distinct red or green labeling indicating that distinct sets of neurons were activated by the different learning and memory contexts. From figure 2 in “Creating a False Memory in the Hippocampus” published July 26, 2013 in Science.

A remarkable study reported this summer in the research article “Creating a False Memory in the Hippocampus” (published July 26, 2013 in Science) received a lot of attention in the popular press. The study deserves our attention because of the elegant experimental techniques the research team developed to help observe and understand memory formation and its effects on behavior.

The type of memory the research team created in mice is known as contextual memory. It’s like memory that makes you feel uneasy when you walk to that corner of the garage where some years ago you stepped on a nail that punctured your foot. You formed a contextual memory with the result that you avoid that particular corner of the garage.

Some mice in this study formed contextual memories associated with active neurons labeled red in a part of the brain known as the dentate gyrus. The same contextual memories were activated in the same set of mice at a later point in time but this time the active neurons were labeled green. Mostly the same neurons were labeled with both red and green (emitting yellow) which indicated that the same contextual memory activated the same set of neurons at different points in time (see Figure 1 above). When mice formed different contextual memories, different sets of neurons were active.

Now here is the how they do the false memory trick. Using fiber optic cables, the scientist can activate just the red subset of neurons using red light or the green subset of neurons using green light. Imagine if the neurons that were active in your brain when you stepped on that nail were labeled in red and then, at some later date, reactivated using red light. That’s what was done in this study. While the mouse was exposed to events that resulted in contextual memory associated with the green labeled neurons, the research team used red light to activate the red labeled neurons. It’s as if you felt uneasy and avoided the sunflower growing in the front yard because, while you stood next to the sunflower, the neurons in your head associated with stepping on the nail in the garage were activated using red light.

These are powerful techniques developed to help us understand the brain. However, notice that we remain a long way from understanding how exactly an active set of neurons results in us feeling uneasy. How it is that this uneasiness is brought to mind? Many have speculated but the step from correlation to experience remains a mystery.