A transgenic mouse model for Alzheimer's disease has impaired synaptic gain but normal synaptic dynamics

The chronic accumulation of amyloid beta (Aβ) peptides is thought to underlie much of the pathology of Alzheimer's disease (AD), and transgenic mice overexpressing Aβ show both behavioral defects and impairments in hippocampal synaptic transmission. In the present study, we examined excitatory transmission at the Schaffer collateral synapse in acute hippocampal slices from APPSwe/PS-1A246E transgenic mice to determine whether the synaptic impairment in these mice is due to a reduction in the activity-independent synaptic gain, or to a change in the activity-dependent synaptic dynamics. We observed a strong reduction in synaptic transmission in slices from APPSwe/PS-1A246E mice compared to those from their wildtype littermates. However, there was no resolvable change in the synaptic dynamics observed in response to either simple or complex stimulus trains. We conclude that the chronic accumulation of Aβ impairs synaptic transmission through a reduction in the synaptic gain, while preserving the synaptic dynamics.

► We examined hippocampal synaptic function in mice overexpressing β-amyloids.
► These mice had profoundly impaired synaptic output at Schaffer collateral synapses.
► The impairment was due to a reduction in the gain of the synaptic output.
► Activity-dependent short-term plasticity was normal over a wide frequency range.