Modification of extracellular matrix by enzymatic removal of chondroitin sulfate and by lack of tenascin-R differentially affects several forms of synaptic plasticity in the hippocampus
Section snippets
Animals
Three- to four-month-old TN-R deficient mice44 with a mixed C57BL/6J×129Ola×129Sv/Ev genetic background (TN-R −/−) and wild-type littermate mice (TN-R +/+) with corresponding genotype were used in experiments investigating the roles of TN-R in synaptic plasticity. Animals were derived from the breeding unit of the University Hospital Eppendorf, Hamburg, Germany. All efforts were made to minimize both the suffering and the number of animals used. All surgical procedures were approved by the
Immunohistochemical control of treatment with chondroitinase ABC
To remove CSs from the tissue, we incubated the slices with chondroitinase ABC.21 Efficacy of treatment was confirmed by immunostaining with monoclonal antibody 473HD for CSs performed for every slice after the end of the physiological recordings. In non-treated slices CSs were expressed in the CA1 area of the hippocampus, with accumulated immunoreactivity in the pyramidal cell layer and the strata orients and lacunosum-moleculare (Fig. 1A). Enzymatically treated slices were morphologically
Discussion
Our study provides evidence that treatment with chondroitinase ABC does not interfere with basal excitatory synaptic transmission and short-term plasticity but reduces LTP in the CA1 region of the hippocampus. Mice deficient in expression of TN-R, one of the binding partners of CSPGs, exhibit a number of abnormalities that are not observed after removal of CS: increased basal excitatory synaptic transmission and significantly reduced short-lasting potentiation and depression. LTP is similarly
Acknowledgements
We thank S. Schmidt for tenascin-R deficient mice, A. Dahlmann for genotyping and W. Anderson for sharing the LTP101M program. This work was supported by Deutsche Forschungsgemeinschaft (SFB 470, to M. S.).
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