Age-related structural and functional modification of cortical synapses

Cortical synaptic atrophy with aging has long been regarded as the primary substrate of decline in cognitive function. However, little is known about the impact of this structural change on cortical synaptic function. The aim of this thesis was to investigate the functional consequence of age-related synaptic reductions in the parietal cortex. In the first study, I analyzed synaptic density in the parietal cortex and revealed significant age-related presynaptic reductions. Interestingly, I found a preferential disappearance of synapses in deep cortical layers. The functional impact of presynaptic reduction was tested in the second study. Whole cell patch clamp recording of spontaneous synaptic currents (sPSCs) onto layer V pyramidal neurons revealed no age-related change. In contrast, the frequency of action potential - independent miniature postsynaptic currents (mPSCs) was decreased, thus revealing an increase in action potential dependent activity (FrequencysPSCs - frequencymPscs) in aged brains. The third study focused on the ratio between excitation and inhibition in aged impaired and aged unimpaired rats that were divided on the basis of their performance in the Morris Water Maze. Interestingly, I found an imbalance between excitation and inhibition in both aged groups. Finally, to test whether similar age-related modifications occur in other neurotransmitter systems, the fourth study contrasted cholinergic vs. non-cholinergic inputs onto layer V pyramidal neurons. I found a preferential decline in cholinergic inputs onto pyramidal neurons with aging. These findings provide evidence of functional compensation for the lost of synaptic structures in aged brains. However, rather than a general decline in synaptic function, imbalance between different synaptic inputs may be an important cellular substrate for cognitive impairment