Periodic Reporting for period 1 - FindMEMO (Functional contribution of visual features to hippocampal memory encoding)
Reporting period: 2019-09-01 to 2021-08-31
Storing and recalling distinct memories are essential brain functions that play key roles in guiding our day-to-day behavior. For example, you may encounter your old school professor whom you have not seen in ten years. His hair is thinner and grayer, he wears different glasses, and has put on some weight. Nonetheless, your brain allows you to retrieve your old memories of this individual even though the inputs are altered. At the same time, you also want to create a distinct, new memory of the individual you have seen today. How can the brain allow both processes (neuronal discrimination and generalization) to occur simultaneously? A brain structure called the hippocampus is thought to be in charge of this task. However, it is still unclear how and where in the hippocampus distinct memories of similar events are formed, and surprisingly little is known about how these memory representations are then used to guide our behavior. In the reporting period of the project FindMEMO, I aimed to address this ambitious key question: How are distinct memories formed and used for behavior?
To address this fundamental question we have measured the activity of populations of neurons in behaving animals and combined imaging and behavioral techniques. We performed experiments of 2-photon calcium imaging, a microscopy technique that allows to observe the activity of individual identified neurons deep in the brain while mice navigate in a virtual reality environment. Mice have been trained to detect small or large differences in the virtual environment (such as a change in the angle of the stripes that cover the walls) by stopping at distinct points along the virtual track to receive a sugar water reward. These experiments have enabled to relate behavioral performance to the activity of neurons in different subregions of the hippocampus. We found that neurons in the entry station of the hippocampus, the dentate gyrus, reliably detect small and large differences between two environments. By contrast, neuronal activity in the output region, called CA1, depends on the degree of differences between environments and reflects the performance in the task. These findings suggest that the dentate gyrus attaches “tags” to different environments depending on external and internal variables, and the downstream circuit CA1 uses this information to form a new memory if the saliency of the new environment is sufficiently large. The resulting distinct memories can then be used to guide behavior.
By linking the behavioural performance of the animal with neuronal responses in the hippocampal input and output structures, my work provided novel insight into the fundamental processes underlying memory formation. It thus reconciles a long debate by explaining why previous studies have led to controversial results about the role of hippocampal regions in memory formation.