Reduced Perisomatic Inhibition, Increased Excitatory Transmission, and Impaired Long-Term Potentiation in Mice Deficient for the Extracellular Matrix Glycoprotein tenascin-R

Mol Cell Neurosci. 2001 Jan;17(1):226-40. doi: 10.1006/mcne.2000.0922.

Abstract

The role of the extracellular matrix molecule tenascin-R (TN-R) in regulation of synaptic transmission and plasticity in the CA1 region of the hippocampus was studied using mice deficient in expression of this molecule. The mutant mice showed normal NMDA-receptor-mediated currents but an impaired NMDA-receptor-dependent form of long-term potentiation (LTP) as compared to wild-type littermates. Reduced LTP in mutants was accompanied by increased basal excitatory synaptic transmission in synapses formed on CA1 pyramidal neurons. A possible mechanism for increased excitatory synaptic transmission in mutants could involve modulation of inhibition, since TN-R and its associated carbohydrate HNK-1 decorate perisomatic interneurons. Indeed, the amplitudes of unitary perisomatic inhibitory currents were smaller in mutants compared to wild-type mice. Thus, our data show that a deficit in TN-R results in reduction of perisomatic inhibition and, as a consequence, in an increase of excitatory synaptic transmission in CA1 to the levels close to saturation, impeding further expression of LTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD57 Antigens / metabolism
  • Glycoproteins / deficiency*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Interneurons / metabolism
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Mutant Strains
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism
  • Receptors, AMPA / metabolism
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / physiology*
  • Tenascin / deficiency*
  • Tenascin / genetics
  • Tenascin / metabolism

Substances

  • CD57 Antigens
  • Glycoproteins
  • Receptors, AMPA
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Tenascin
  • tenascin R