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Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

Marianna Szemes1, Rachel L Davies2, Claire LP Garden3 and Maria M Usowicz4*

Author Affiliations

1 Present address: School of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, UK

2 Present address: Research & Enterprise Development, University of Bristol, Senate House, Tyndall Avenue, Bristol BS8 1TH, UK

3 Present address: School of Life, Sport and Social Sciences, Edinburgh Napier University, Sighthill Court, Edinburgh EH11 4BN, UK

4 School of Physiology & Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK

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Molecular Brain 2013, 6:33  doi:10.1186/1756-6606-6-33

Published: 19 July 2013



Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels.


We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ).


Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS.

Down syndrome; Down’s syndrome; Cerebellum; Ts65Dn; Granule cell; GABAA receptor; Tonic inhibition; Shunting; qPCR; Single-cell RT-PCR