Strain differences in hippocampal synaptic dysfunction in the TgCRND8 mouse model of Alzheimer's disease:...

In Alzheimer's disease (AD), characterized by cognitive deterioration, synaptic alterations are frequently reported. The TgCRND8 model, in which mice develop AD-like amyloid β plaque formation, has been used to investigate the effects of amyloidosis on synaptic function. Background strain impacts the behavioral and neuropathological phenotype of mice in this model, but whether this extends to synaptic function is unknown. We investigated the influence of background strain on basal synaptic transmission and long-term potentiation (LTP) in the hippocampus of TgCRND8 mice (13-16 months) on hybrid backgrounds of (129SvEv/Tac) x (C3H/C57/129SvEv/Tac) (aka "129") or (C57) x (C3H/C57) (aka "C3H"). In littermate controls, basal synaptic transmission was significantly reduced, whereas the amplitude of excitatory postsynaptic potentials was significantly higher after LTP induction in 129 vs. C3H mice. In 129 TgCRND8 mice, deficits in hippocampal LTP were more severe than in C3H TgCRND8 relative to controls. Compared to controls, network excitability was decreased in transgenics from both strains. These data suggest that 129 TgCRND8 mice are the more appropriate model to evaluate the efficacy of potential AD treatments on synaptic function, owing to their significant deficit in LTP. Such studies are critical in order to improve the translational capacity of basic science research.