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Syndecan-3-Deficient Mice Exhibit Enhanced LTP and Impaired Hippocampus-Dependent Memory

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Abstract

Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated manner. Syndecan-3 has been suggested to play a role in the development and plasticity of neuronal connections by linking extracellular signals to the regulation of the cytoskeleton. To study its physiological functions, we produced mice deficient in syndecan-3 by gene targeting. The mutant animals are healthy, are fertile, and have no apparent defects in the structure of the brain. We focused on characterizing the functions of the hippocampus, a brain area where expression of syndecan-3 is prominent in adults. Mice lacking syndecan-3 exhibited an enhanced level of long-term potentiation (LTP) in area CA1, while basal synaptic transmission and short-term plasticity were similar to those in wild-type animals. Further, the mutant mice were not responsive to the syndecan-3 ligand heparin-binding growth-associated molecule, which inhibits LTP in area CA1 in wild-type animals. Behavioral testing of the syndecan-3-deficient mice revealed impaired performance in tasks assessing hippocampal functioning. We suggest that syndecan-3 acts as an important modulator of synaptic plasticity that influences hippocampus-dependent memory.

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    1

    These authors contributed equally to this work.

    2

    Current address: Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.

    3

    Current address: A. I. Virtanen Institute for Molecular Sciences, BioTeknia, Neulaniementie 2, 70210 Kuopio, Finland.

    4

    To whom correspondence should be addressed at the Laboratory of Molecular Neurobiology, Institute of Biotechnology and Department of Biosciences, P.O. Box 56 (Viikinkaari 5), FIN-00014 University of Helsinki, Finland. Fax: +358 9 191 59068. E-mail: [email protected].

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