Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice.
Mice carrying mutated human APPswe and PS1 (A246E) transgenes (A/P mice) show age-dependent memory impairment in hippocampus-dependent tasks. Moreover, the mice show normal learning in the water maze within a day but impairment across days. We recorded LTP in a slice preparation (CA1) and in chronically implanted animals (dentate gyrus, or DG) at 17-18 months of age. The genotypes did not differ in the basal synaptic transmission. Also, LTP induction and its maintenance over 60 min did not differ between A/P and control mice. However, the fEPSP enhancement in vivo decayed to 77% of its maximum in 24 h in A/P mice while remaining at 96% in control mice. The time course of the LTP decay in the A/P mice corresponds to their behavioral impairment and indicates that Abeta accumulation in the dentate gyrus may interfere with the signal transduction pathways responsible for memory consolidation.
Department of Neuroscience and Neurology, University of Kuopio, 70211 Kuopio, Finland.
I
I
Gureviciene
S
S
Ikonen
K
K
Gurevicius
A
A
Sarkaki
T
T
van Groen
R
R
Pussinen
A
A
Ylinen
H
H
Tanila
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1; D009435:Synaptic Transmission / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1