Tenascin-R-deficient mice show structural alterations of symmetric perisomatic synapses in the CA1 region of the hippocampus

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Abstract
Accumulating evidence suggests that extracellular matrix (ECM) molecules play important roles in formation of synapses. Our previous electrophysiologic study of mice deficient in the extracellular matrix glycoprotein tenascin-R (TN-R) showed an impaired γ-aminobutyric acid release at perisomatic inhibitory synapses in the CA1 pyramidal cell layer of the hippocampus. The present study investigated possible ultrastructural correlates of abnormal perisomatic inhibition. Topographic, morphometric, and stereologic methods were applied at the light and electron microscopic levels to quantify the density and spatial arrangement of cell bodies of CA1 pyramidal neurons and density and architecture of symmetric synapses formed on them in TN-R−/− and wild-type mice of different ages. The spatial arrangement of neuronal cell bodies in the CA1 pyramidal cell layer was found more diffuse and disordered in TN-R−/− mice than in wild-type animals. The coverage of the plasma membrane of pyramidal cell bodies by active zones of symmetric synapses was reduced by at least 40% in TN-R−/− animals compared with control animals. Further, the length of active zone profiles of perisomatic inhibitory synapses in the CA1 pyramidal cell layer was 8–14% smaller, whereas the number of active zones calculated per length unit of cell body profile was 30–40% smaller in TN-R mutants than in wild-type animals. The density and spatial arrangement of synaptic vesicles in the synaptic terminals provided ultrastructural evidence for reduced synaptic activity in TN-R mutants. Thus, TN-R appears to play an important role in the regulation of the number and architecture of perisomatic inhibitory synapses, which play crucial roles in the synchronization of neuronal activity and modulation of synaptic plasticity in the hippocampus. J. Comp. Neurol. 456:338–349, 2003.
Funding Information
  • European Molecular Biology Organization (ASTF9875)
  • Deutsche Forschungsgemeinschaft (BR 1208/3-1, SCHA185/29-1)