FINAL ACCEPTED VERSION Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice

Hippocampal slices obtained from C57BL/6 mice (3 to 25 months in age) were used to investigate the effects of aging on EPSPs (excitatory postsynaptic potentials) elicited in dentate gyrus with lateral perforant path stimulation. The maximal amplitude of the EPSP, as well as the degree of paired-pulse facilitation, were significantly reduced in animals aged 12 months or more, as compared to younger animals (<12 months). Although all animals showed equivalent short-term potentiation (STP) in response to high frequency stimulation, this did not translate into a long-lasting increase in synaptic efficacy in the older animals. A significant degree of long-term potentiation (LTP) of synaptic efficacy was only observed in animals less than 12 months of age when measured 30 minutes post-induction. Blocking GABAA mediated inhibition significantly enhanced STP in younger and older animals, however a significant degree of LTP was again only observed in slices taken from younger animals. These data indicate that the lateral perforant path input to the dentate gyrus is altered by the aging process, and that this results in a reduction in the capacity of this input to exhibit long-lasting synaptic plasticity.