Basement membrane protein nidogen-1 shapes hippocampal synaptic plasticity and excitability.
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.
Vasudevan
Anju
A
Center for Biochemistry and Center for Molecular Medicine Cologne, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, Germany.
Ho
Matthew S P
MS
Weiergräber
Marco
M
Nischt
Roswitha
R
Schneider
Toni
T
Lie
Ailing
A
Smyth
Neil
N
Köhling
Rüdiger
R
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009068:Movement; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D000091042:Reelin Protein; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
C114785:2-amino-4-phosphono-propinate; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; D011422:Propionates; D000091042:Reelin Protein; C089141:laminin gamma 1; C029967:nidogen; C000717128:Reln protein, mouse