Synaptic numbers across cortical laminae and cognitive performance of the rat during ageing.

In this study, we have investigated the changes in the number of individual presynaptic boutons in the neocortex of rats and correlated them with cognitive performance. Brown Norway x Fischer 344 F1 hybrid rats, aged from one to 24 months, were used. Using synaptophysin as a marker for presynaptic boutons, we found that in the parietal II region of the neocortex an age-related decrease in the density of immunostained punctae representing presynaptic boutons occurred. Regression analysis showed that this decline in the number of presynaptic boutons correlates with ageing (r=0.495, P<0.05). Interestingly, we found that this age-related depletion of presynaptic boutons was more intense in the deeper cortical lamina, such as laminae V and VI (mean decrease of 18%), than in the superficial laminae (mean decrease of 8% in laminae I-IV). Using the Morris water maze test, we observed that young rats acquired the task at twice the speed of aged animals (48.9 +/- 9.0 s and 91.0 +/- 4.9 s for young and aged animals, respectively). Furthermore, at the end of the training period, the aged cohort still showed significantly higher escape latencies in the Morris water maze. The present findings support the concept that the decline in cognitive performances in ageing is related to the loss of synapses in the cerebral cortex.