The role of mesocortical projections in age-related cognitive decline – DOPAGE

Mesocortical projections from the ventral tegmental area to the prefrontal cortex are suggested to participate in working memory cognitive decline. The DOPAGE project will investigate through in-depth behavioral and anatomical analysis the involvement of mesocortical neurons in age-related cognitive decline in both male and female mice. We hypothesize subtle compensatory changes in mesocortical neurons underlie inter-individual differences in WM performance in older individuals. We will characterize the functional involvement of two subpopulations of mesocortical inputs : dopamine and glutamate neurons. We will investigate their respective functional roles through optogenetics, in order to rescue WM performance in cognitively impaired individuals and provide a mechanism underlying inter-individual differences during aging. Overall, our project will provide knowledge on how aging affects mesocortical cellular subpopulations in both sexes and how those may participate in working memory deficits.