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Mice with astrocyte-directed inactivation of connexin43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels

Authors

  • Christian Frisch,

    1. Institute of Physiological Psychology, and Center for Biological and Medical Research, Heinrich Heine-University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany
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    • Present address : Department of Epileptology, Friedrich-Wilhelms-University of Bonn, Sigmund Freud-Strasse 25, D-53105 Bonn, Germany.

  • Martin Theis,

    1. Institute of Genetics, Friedrich-Wilhelms-University of Bonn, Römerstraße 164, D-53117 Bonn, Germany
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    • Present address : Howard Hughes Medical Institute, Center for Neurobiology and Behaviour, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.

  • Maria A. De Souza Silva,

    1. Institute of Physiological Psychology, and Center for Biological and Medical Research, Heinrich Heine-University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany
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  • Ekrem Dere,

    1. Institute of Physiological Psychology, and Center for Biological and Medical Research, Heinrich Heine-University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany
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  • Goran Söhl,

    1. Institute of Genetics, Friedrich-Wilhelms-University of Bonn, Römerstraße 164, D-53117 Bonn, Germany
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  • Barbara Teubner,

    1. Institute of Genetics, Friedrich-Wilhelms-University of Bonn, Römerstraße 164, D-53117 Bonn, Germany
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  • Katerina Namestkova,

    1. Department of Neuroscience, Institute of Experimental Medicine ASCR, Videnska 1083, 142 20 Prague 4, Czech Republic
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  • KIaus Willecke,

    1. Institute of Genetics, Friedrich-Wilhelms-University of Bonn, Römerstraße 164, D-53117 Bonn, Germany
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  • Joseph P. Huston

    1. Institute of Physiological Psychology, and Center for Biological and Medical Research, Heinrich Heine-University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany
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: Dr Christian Frisch, 1 Institute of Physiological Psychology, as above.
E-mail: chfrisch@uni-duesseldorf.de

Abstract

Gap junctions mediate communication between many cell types in the brain. Gap junction channels are composed of membrane-spanning connexin (Cx) proteins, allowing the cell-to-cell passage of small ions and metabolites. Cx43 is the main constituent of the brain-spanning astrocytic gap junctional network, controlling activity-related changes in ion and glutamate concentrations as well as metabolic processes. In astrocytes, deletion of Cx43-coding DNA led to attenuated gap junctional coupling and impaired propagation of calcium waves, known to influence neuronal activity. Investigation of the role of Cx43 in behaviour has been impossible so far, due to postnatal lethality of its general deletion. Recently, we have shown that deletion of Cx30, which is also expressed by astrocytes, affects exploration, emotionality, and neurochemistry in the mouse. In the present study, we investigated the effects of the astrocyte-directed inactivation of Cx43 on mouse behaviour and brain neurochemistry. Deletion of Cx43 in astrocytes increased exploratory activity without influencing habituation. In the open field, but not in the elevated plus-maze, an anxiolytic-like effect was observed. Rotarod performance was initially impaired, but reached control level after further training. In the water maze, Cx43 deficient mice showed a steeper learning course, although final performance was similar between groups. Cx43 inactivation in astrocytes increased acetylcholine content in the frontal cortex of water maze-trained animals. Results are discussed in terms of altered communication between astrocytes and neurons, possible compensation processes, and differential effects of Cx30- and astrocyte-specific Cx43 deletion.

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