Elsevier

Neuroscience

Volume 104, Issue 2, 10 May 2001, Pages 359-369
Neuroscience

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

https://doi.org/10.1016/S0306-4522(01)00082-3Get rights and content

Abstract

The extracellular matrix is a complex network of macromolecules including glycoproteins, polysaccharides and proteoglycans. Tenascin-R and chondroitin sulfate proteoglycans are essential components of hippocampal extracellular matrix co-localised in perineuronal nets on interneurons. Mutant mice deficient in expression of tenascin-R showed a two-fold reduction of long-term potentiation induced by theta-burst stimulation of Schaffer collaterals in the stratum radiatum of the CA1 region of the hippocampus, as compared to wild-type mice. The same reduction in potentiation was observed in slices from wild-type mice pretreated for 2 h with chondroitinase ABC that completely removed chondroitin sulfates from the extracellular matrix. Treatment of slices from tenascin-R deficient animals with the enzyme did not further reduce potentiation in comparison with untreated slices from these mice, showing an occlusion of effects produced by removal of tenascin-R and chondroitin sulfates. However, the level of potentiation recorded immediately after theta-burst stimulation was significantly higher in wild-type than in tenascin-R deficient mice, whereas chondroitinase ABC had no significant effect on this short-term form of plasticity. Enzymatic treatment also did not affect short-term depression evoked by low-frequency stimulation, whereas this form of synaptic plasticity was reduced in tenascin-R deficient mice. In contrast, long-term depression in CA1 was impaired by digestion of chondroitin sulfates but appeared normal in tenascin-R mutants.

Our data demonstrate that tenascin-R and chondroitin sulfate proteoglycans differentially modulate several forms of synaptic plasticity, suggesting that different mechanisms are involved.

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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