Age-Related Changes in Synaptic Transmission in Cognitive Design

Cognitive decline is considered an inevitable consequence of ageing with human brain-imaging studies suggesting that functional changes in connectivity underlies this decline. My laboratory is exploring the hypothesis that cognitive decline is caused by changes in the number and/or the strength of synaptic connections. I will briefly describe the longitudinal behavioural strategies we use to monitor changes in cognitive performance. I will then introduce the automated two-photon imaging and 3D tomography techniques we have developed to trace neuronal connections. Finally, I will discuss the feasibility of combining mGRASP (mammalian GFP reconstitution across synaptic partners) with optogenetics to reveal age-related differences in the synaptic weighting of defined neuronal projections. The aim of this work is to better understand the changes taking place in the brain that could explain the inevitable cognitive decline that is associated with ageing.