Early temporal short-term memory deficits in double transgenic APP/PS1 mice |
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Authors: | Saioa LagadecLolita Rotureau,Agnè s Hé marNathalie Macrez,Sebastien DelcassoYannick Jeantet,Yoon H. Cho |
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Affiliation: | a CNIC, CNRS UMR 5228, Université Bordeaux 1, France b UMR, 5091 CNRS, Institut François Magendie, Université Victor Ségalen Bordeaux 2, France |
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Abstract: | We tested single APP (Tg2576) transgenic, PS1 (PS1dE9) transgenic, and double APP/PS1 transgenic mice at 3 and 6 months of age on the acquisition of a hippocampal-dependent operant “differential reinforcement of low rate schedule” (DRL) paradigm. In this task mice are required to wait for at least 10 seconds (DRL-10s) between 2 consecutive nose poke responses. Our data showed that while single APP and PS1 transgene expression did not affect DRL learning and performance, mice expressing double APP/PS1 transgenes were impaired in the acquisition of DRL-10s at 6 months, but not at 3 months of age. The same impaired double transgenic mice, however, were perfectly capable of normal acquisition of signaled DRL-10s (SDRL-10s) task, a hippocampal-independent task, wherein mice were required to emit responses when the end of the 10-second delay was signaled by a lighting of the chamber. The age-dependent and early deficits of APP/PS1 mice suggest that the appetitive DRL paradigm is sensitive to the amyloid pathology present in double APP/PS1 mice, and that this mouse line represents a good model with which to study the efficacy of therapeutic strategies against Alzheimer's disease. |
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Keywords: | Operant learning DRL Short-term memory Tg2576 PS1dE9 Amyloid precursor protein Presenilin 1 Hippocampus |
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