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Basement membrane protein nidogen‐1 shapes hippocampal synaptic plasticity and excitability
Author(s) -
Vasudevan Anju,
Ho Matthew S.P.,
Weiergräber Marco,
Nischt Roswitha,
Schneider Toni,
Lie Ailing,
Smyth Neil,
Köhling Rüdiger
Publication year - 2010
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20660
Subject(s) - neuroscience , hippocampal formation , dentate gyrus , long term potentiation , synaptic plasticity , perforant path , laminin , chemistry , extracellular matrix , biology , microbiology and biotechnology , receptor , biochemistry
The basement membrane (BM) is a specialized form of extracellular matrix (ECM) underlying epithelia and endothelia and surrounding many types of mesenchymal cells. Nidogen, along with collagen IV and laminin, is a major component of BMs. Although certain ECM proteins such as laminin or reelin influence neuronal function via interactions with cell‐surface receptors such as integrins, behavioral neurological impairments due to deficits of BM components have been recognized only recently. Here, alterations in neuronal network function underlying these behavioral changes are revealed. Using nidogen‐1 knockout mice, with or without additional heterozygous nidogen‐2 knockout ( NID1 −/− / NID2 +/+ or NID1 −/− / NID2 ± ), we demonstrate that nidogen is essential for normal neuronal network excitability and plasticity. In nidogen‐1 knockouts, seizurelike behavior occurs, and epileptiform spiking was seen in hippocampal in vivo EEG recordings. In vitro, hippocampal field potential recordings revealed that lack of nidogen‐1, while not causing conspicuous morphological changes, led to the appearance of spontaneous and evoked epileptiform activity, significant increase of the input/output ratio of synaptically evoked responses in CA1 and dentate gyrus, as well as of paired pulse accentuation, and loss of perforant‐path long‐term synaptic potentiation. Nidogen‐1 is thus essential for normal network excitability and plasticity. © 2009 Wiley‐Liss, Inc.