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

Neuroscience. 2001;104(2):359-69. doi: 10.1016/s0306-4522(01)00082-3.


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 2h 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Chondroitin ABC Lyase / pharmacology*
  • Chondroitin Sulfates / deficiency*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Immunohistochemistry
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Knockout
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tenascin / deficiency*
  • Tenascin / genetics


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Tenascin
  • tenascin R
  • 2-Amino-5-phosphonovalerate
  • Chondroitin Sulfates
  • Chondroitin ABC Lyase