Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome.
Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21). Recently, O'Doherty and colleagues in an earlier study generated a new genetic mouse model of DS (Tc1) that carries an almost complete Hsa21. Since DS is the most common genetic cause of mental retardation, we have undertaken a detailed analysis of cognitive function and synaptic plasticity in Tc1 mice. Here we show that Tc1 mice have impaired spatial working memory (WM) but spared long-term spatial reference memory (RM) in the Morris watermaze. Similarly, Tc1 mice are selectively impaired in short-term memory (STM) but have intact long-term memory (LTM) in the novel object recognition task. The pattern of impaired STM and normal LTM is paralleled by a corresponding phenotype in long-term potentiation (LTP). Freely-moving Tc1 mice exhibit reduced LTP 1 h after induction but normal maintenance over days in the dentate gyrus of the hippocampal formation. Biochemical analysis revealed a reduction in membrane surface expression of the AMPAR (alpha-amino-3-hydroxy-5-methyl-4-propionic acid receptor) subunit GluR1 in the hippocampus of Tc1 mice, suggesting a potential mechanism for the impairment in early LTP. Our observations also provide further evidence that STM and LTM for hippocampus-dependent tasks are subserved by parallel processing streams.
Morice
Elise
E
Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom. elise.morice@u-psud.fr
Andreae
Laura C
LC
Cooke
Sam F
SF
Vanes
Lesley
L
Fisher
Elizabeth M C
EM
Tybulewicz
Victor L J
VL
Bliss
Timothy V P
TV
D000704:Analysis of Variance; D000818:Animals; D002891:Chromosomes, Human, Pair 21; D004193:Discrimination Learning / Q000502:physiology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004594:Electrophysiology; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology*; D046709:Pattern Recognition, Physiological / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology; D014314:Trisomy
D018091:Receptors, AMPA