To investigate whether the spine loss in APP−/− mice is correlated with impairment in synaptic function, we examined LTP, basal synaptic transmission, and the paired-pulse facilitation in both old (~13 months old) and young (2-4 months old) animals. LTP was measured after tetanic stimulation by four trains of 1-s 100 Hz stimulations. We saw a marked impairment in LTP in old APP−/− mice as compared to controls but not in young APP−/− (Fig. 4A, B). The slope of fEPSP in the old APP +/− was 296.47 ± 6.07% compared to 134.83 ± 4.52% in the APP−/− mice 60 minutes after LTP induction (Fig. 4A). Consistent with the in vivo morphological studies, there was no impairment in LTP in young APP KO mice as seen in the old animals (Fig. 4B). The basal transmissions were examined by plotting the input-output (I-O) curve (fiber volley against fEPSP slope). There was no difference in input/output ratio of APP+/− vs. APP−/− at either age group (Fig. 4C, D). Thus the reduction in LTP was not mirrored by changes in basal synaptic transmission. Finally, paired-pulse
