Reduction in size of perforated postsynaptic densities in hippocampal axospinous synapses and age-related spatial learning impairments

J Neurosci. 2004 Sep 1;24(35):7648-53. doi: 10.1523/JNEUROSCI.1725-04.2004.


A central problem in the neurobiology of normal aging is why learning is preserved in some aged individuals yet impaired in others. To investigate this issue, we examined whether age-related deficits in spatial learning are associated with a reduction in postsynaptic density (PSD) area in hippocampal excitatory synapses (i.e., with a structural modification that is likely to have a deleterious effect on synaptic function). A hippocampus-dependent version of the Morris water maze task was used to separate Long-Evans male rats into young adult, aged learning-unimpaired, and equally aged learning-impaired groups. Axospinous synapses from the CA1 stratum radiatum were analyzed using systematic random sampling and serial section analyses. We report that aged learning-impaired rats exhibit a marked ( approximately 30%) and significant reduction in PSD area, whereas aged learning-unimpaired rats do not. The observed structural alteration involves a substantial proportion of perforated synapses but is not observed in nonperforated synapses. These findings support the notion that many hippocampal perforated synapses become less efficient in aged learning-impaired rats, which may contribute to cognitive decline during normal aging.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / pathology*
  • Animals
  • Hippocampus / pathology*
  • Learning Disabilities / pathology*
  • Male
  • Maze Learning
  • Memory Disorders / pathology*
  • Microscopy, Electron
  • Organelles / ultrastructure
  • Rats
  • Rats, Long-Evans
  • Single-Blind Method
  • Synaptic Membranes / ultrastructure*