Various animal models of Alzheimer disease (AD) are cha- racterized by deficits in spatial memory that are causally related to altered synaptic function and impairment of long-term potentiation (LTP) in the hippocampus. In Tg2576 AD mice, we compared LTP in 2 major hippocampal path- ways, Schaffer collateral (SC) and mossy fiber (MF) pathways. Whereas LTP was completely abolished in the SC pathway of Tg2576 mice, we found no decrease in LTP induced by stimulation of the MF pathway. In fact, we found that in the MF pathway, LTP was slightly, but sig-nificantly, enhanced compared with that in the MF pathway of WT littermates. This pathway-specific impair-ment of LTP is not attributable to alterations in transmitter release, as indicated by an unaltered paired-pulse ratio. These results suggest that the spatial memory deficits normally seen in AD models arise primarily from LTP im-pairment at the SC pathway.

Keywords: Alzheimer’s disease, long-term potentiation, mossy fiber pathway, schaffer collateral pathway, Tg2576