Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome
- Elise Morice1,4,6,
- Laura C. Andreae1,
- Sam F. Cooke1,5,
- Lesley Vanes2,
- Elizabeth M.C. Fisher3,
- Victor L.J. Tybulewicz2, and
- Timothy V.P. Bliss1
- 1 Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom;
- 2 Division of Immune Cell Biology, National Institute for Medical Research, London NW7 1AA, United Kingdom;
- 3 Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
Abstract
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 (α-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.
Footnotes
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↵4 Present addresses: Laboratoire de Neurobiologie de l’Apprentissage, de la Mémoiré et de la Communication (NAMC), CNRS UMR 8620, Université Paris-Sud, 91405 Orsay Cedex, France;
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↵5 The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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↵6 Corresponding author.
↵6 E-mail elise.morice@u-psud.fr; fax 33-169157725.
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Article is online at http://www.learnmem.org/cgi/doi/10.1101/lm.969608.
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- Received February 19, 2008.
- Accepted May 6, 2008.
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Freely available online through the Learning & Memory Open Access option.
- Copyright © 2008, Cold Spring Harbor Laboratory Press