Memory engram pathology and underlying cellular and molecular alterations in Down syndrome

The mechanisms underlying Down syndrome (DS) memory deficits are still unknown. New technologies enable the visualization and manipulation of the neural correlates of memory, the so-called memory engrams, which are sparse groups of cells that activate upon learning and reactivate during memory recall. Few studies have examined memory engram pathology in cognitive disorders, and no studies have explored engram formation, maintenance and reactivation in intellectual disability. Previous work from the laboratory of Mara Dierssen discovered neuronal and synaptic signaling alterations suggesting that DS is a model of inherently defective engrams. Thus, their goal is to understand whether engrams can form and reactivate in DS rodent models, by tagging and manipulating specific engram cells. Researchers will identify perturbations in the DS engram and assess if pro-cognitive therapies are able to reverse them. In brief, the project will seek the understanding of how specific alterations make DS neurons less suitable for allocation to an engram and therefore lead to impaired engram formation.