Synaptic transmission was studied in hippocampal slices from aged (12-14 months of age) TAS10 mice overexpressing the human form of the amyloid precursor protein harboring the Swedish mutation. A significant deficit in the input-output relationship of glutamatergic synapses in the CA3-CA1 Schaffer collateral pathway was observed, while synaptic transmission in the medial perforant pathway of the dentate gyrus was comparatively preserved. Despite this deficit, relative levels of short-and long-term synaptic plasticity in the CA1 region were similar to those observed in wildtype slices. Specifically, paired pulse facilitation, frequency facilitation (at frequencies of 1, 5, and 10 Hz), and long-term potentiation induced by a theta burst stimulation paradigm were all normal in the CA3-CA1 synapses of TAS10 hippocampal slices. However, synchronized network activity induced by bath application of 4-aminopyridine (4-AP) was compromised. Thus, the frequency of synchronous events induced by 100 M 4-AP was significantly lower in TAS10 hippocampal slices (inter-event interval: WT, 2.4 ุ 0.6 s; TAS10, 6.9 ุ 1.7 s). To study โฅ-aminobutyric acid (GABA)ergic synaptic transmission NBQX (20 M) and D-AP5 (50 M) were added in order to isolate bicuculline-sensitive GABA-mediated synchronous network activity. The GABAergic network activity was not significantly different from wildtype in terms of frequency. This study suggests that the deficit in glutamatergic synaptic transmission observed in the TAS10 hippocampal slices, may be coupled with alterations in synchronous network activity, which in turn would lead to deficient information processing.