Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice

Alterations in neuronal morphology occur in the brain during normal aging, but vary depending on neuronal cell types and brain regions. Such alterations have been related to memory and cognitive impairment. Changes in hippocampal spine densities are thought to represent a morphological correlate of altered brain functions associated with hippocampal-dependent learning and memory. We therefore have analyzed the impact of aging on different hippocampal-dependent learning tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We found a significant decrease in spine numbers of basal CA1 dendrites and decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons. Furthermore, aged mice exhibited significant deficits in hippocampus-dependent learning tasks, such as the probe trial of the Morris water maze and T maze learning. Given the fact that there is no neuronal loss in the hippocampus in aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434-2440), we suggest that the memory and cognitive decline in the context of aging may be accompanied by rather subtle anatomical changes, such as numbers and morphology of dendritic spines.