Cognitive impairment and transmitter-specific pre- and postsynaptic changes in the rat cerebral cortex during ageing.

Recent studies suggest that age-related cognitive decline is correlated with an excitatory-inhibitory imbalance in synaptic discharges on pyramidal neurons. This study focuses on whether ageing and cognitive status correlates with relative numbers of excitatory and inhibitory presynaptic boutons. We investigated the density of excitatory and inhibitory presynaptic inputs across several areas of the rat cerebral cortex in young and aged male Fischer 344 rats. Aged animals were segregated into aged cognitively impaired (AI) and aged cognitively unimpaired (AU) groups using the Morris water maze. We applied immunohistochemistry to reveal the majority of excitatory and inhibitory presynaptic boutons captured with confocal microscopy and quantitative image analysis. A gradual decline in the density of excitatory and inhibitory presynaptic boutons occurred from young to AU to AI animals; however, the ratios of excitatory to inhibitory presynaptic bouton densities were not significantly altered. We further investigated the density of receptor scaffolding proteins representing key excitatory and inhibitory receptor postsynaptic sites, using antibodies against specific markers of excitatory and inhibitory postsynaptic densities, respectively. Significant changes in the ratios of excitatory to inhibitory postsynaptic densities were observed only in AI compared to young rats.