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 hippocampal slices from young and aged transgenic mice over-expressing a mutant form of the human amyloid precursor protein (PDAPP mice). The transgenic mice at 4-5 months of age, prior to the formation of amyloid-beta peptide deposits in these animals, differed from non-transgenic control mice in three respects: (1) paired-pulse facilitation (PPF) was enhanced; (2) responses to high frequency stimulation bursts were distorted; (3) long-term potentiation (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 exhibit numerous amyloid plaques, neuritic dystrophy, and gliosis. Control mice 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 evidence, although direct comparisons of its induction conditions in aged transgenic and control mice were compromised by the profound differences in field potentials between the two groups. These results point to two conclusions: (1) altered synaptic communication appears in PDAPP mice in advance of amyloid plaque formation and probably involves changes in presynaptic calcium kinetics; (2) the disturbances in synaptic transmission that appear when abundant plaques and Alzheimer's-like neuropathology are present in the transgenic mice are not necessarily accompanied by a disproportionate loss of long-term synaptic plasticity.
Larson
J
J
Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA. jrlarson@psych.uic.edu
Lynch
G
G
Games
D
D
Seubert
P
P
D000375:Aging / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D058225:Plaque, Amyloid / Q000473:pathology; D009435:Synaptic Transmission / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor