Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice

Synaptic transmission and plasticity were studied in the CA1 field of hippo campal slices from young and aged transgenic mice over-expressing a mutant form of the human amyloid precursor protein (PDAPP mice). The transgenic mi ce at 4-5 months of age, prior to the formation of amyloid-beta peptide dep osits in these animals, differed from non-transgenic control mice in three respects: (1) paired-pulse facilitation (PPF) was enhanced; (2) responses t o high frequency stimulation bursts were distorted; (3) long-term potentiat ion (LTP) decayed more rapidly. More striking was the profound reduction in the size of synaptic responses and frequent loss of field potentials that were found in the transgenic mice at 27-29 months, an age at which they exh ibit numerous amyloid plaques, neuritic dystrophy, and gliosis. Control mic e at these ages did not show such dramatic effects. PPF was reduced in aged transgenic mice, compared to aged controls; however, LTP was still in evid ence, although direct comparisons of its induction conditions in aged trans genic and control mice were compromised by the profound differences in fiel d potentials between the two groups. These results point to two conclusions : (1) altered synaptic communication appears in PDAPP mice in advance of am yloid plaque formation and probably involves changes in presynaptic calcium kinetics; (2) the disturbances in synaptic transmission that appear when a bundant plaques and Alzheimer's-like neuropathology are present in the tran sgenic mice are not necessarily accompanied by a disproportionate loss of l ong-term synaptic plasticity. (C) 1999 Elsevier Science B.V. All rights res erved.