Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.

Autor: Witton J; School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK., Padmashri R; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK., Zinyuk LE; School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK., Popov VI; Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Reg. 142290, Russia.; The Open University, Department of Life Sciences, Walton Hall, Milton Keynes, MK7 6AA, UK., Kraev I; The Open University, Department of Life Sciences, Walton Hall, Milton Keynes, MK7 6AA, UK., Line SJ; Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK., Jensen TP; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK., Tedoldi A; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK., Cummings DM; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK., Tybulewicz VLJ; MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK., Fisher EMC; Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK., Bannerman DM; Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, UK., Randall AD; School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK., Brown JT; School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK., Edwards FA; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK., Rusakov DA; Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.; Laboratory of Brain Microcircuits, Institute of Biology and Biomedicine, University of Nizhny Novgorod, Nizhny Novgorod 603950, Russia., Stewart MG; The Open University, Department of Life Sciences, Walton Hall, Milton Keynes, MK7 6AA, UK., Jones MW; School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2015 Sep; Vol. 18 (9), pp. 1291-1298. Date of Electronic Publication: 2015 Aug 03.
DOI: 10.1038/nn.4072
Abstrakt: Hippocampal pathology is likely to contribute to cognitive disability in Down syndrome, yet the neural network basis of this pathology and its contributions to different facets of cognitive impairment remain unclear. Here we report dysfunctional connectivity between dentate gyrus and CA3 networks in the transchromosomic Tc1 mouse model of Down syndrome, demonstrating that ultrastructural abnormalities and impaired short-term plasticity at dentate gyrus-CA3 excitatory synapses culminate in impaired coding of new spatial information in CA3 and CA1 and disrupted behavior in vivo. These results highlight the vulnerability of dentate gyrus-CA3 networks to aberrant human chromosome 21 gene expression and delineate hippocampal circuit abnormalities likely to contribute to distinct cognitive phenotypes in Down syndrome.
Databáze: MEDLINE