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

The extracellular matrix is a complex network of macromolecules including g lycoproteins, polysaccharides and proteoglycans. Tenascin-R and chondroitin sulfate proteoglycans are essential components of hippocampal extracellula r matrix co-localised in perineuronal nets on interneurons. Mutant mice def icient 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 f rom wild-type mice pretreated for 2 h with chondroitinase ABC that complete ly removed chondroitin sulfates from the extracellular matrix. Treatment of slices from tenascin-a deficient animals with the enzyme did not further r educe potentiation in comparison with untreated slices from these mice, sho wing an occlusion of effects produced by removal of tenascin-R and chondroi tin sulfates. However, the level of potentiation recorded immediately after theta-burst stimulation was significantly higher in wild-type than in tena scin-R deficient mice, whereas cbondroitinase ABC had no significant effect on this short-term form of plasticity. Enzymatic treatment also did not af fect short-term depression evoked by low-frequency stimulation, whereas thi s farm of synaptic plasticity was reduced in tenascin-R deficient mice. In contrast, long-term depression in CA1 was impaired by digestion of chondroi tin 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 th at different mechanisms are involved. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.