Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C

Matthias R. Evers, Benedikt Salmen, Olena Bukalo, Astrid Rollenhagen, Michael R. Bösl, Fabio Morellini, Udo Bartsch, Alexander Dityatev, Melitta Schachner

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123 Scopus citations

Abstract

The extracellular matrix glycoprotein tenascin-C (TN-C) has been suggested to play important functional roles during neural development, axonal regeneration, and synaptic plasticity. We generated a constitutively TN-C-deficient mouse mutant from embryonic stem cells with a floxed tn-C allele, representing a standard for future analysis of conditionally targeted mice. The gross morphology of the CNS was not detectably affected, including no evidence for perturbed nerve cell migration, abnormal oligodendrocyte distribution, or defective myelination. Despite the apparent normal histology of the hippocampus and normal performance in the water maze, theta-burst stimulation (TBS) of Schaffer collaterals elicited reduced long-term potentiation (LTP) in the CA1 region of TN-C-deficient mutants, as compared with wild-type littermates. However, high-frequency stimulation evoked normal LTP not only in CA1, but also at mossy fiber-CA3 and medial and lateral perforant path-granule cell synapses in the dentate gyrus. Low-frequency stimulation failed to induce long-term depression in the CA1 region of TN-C-deficient animals. Recordings of TBS-induced LTP in the presence of nifedipine, an antagonist of L-type voltage-dependent Ca2+ channels (VDCCs), did not affect LTP in TN-C-deficient mice, but reduced LTP in wild-type mice to the levels seen in mutants. Furthermore, chemical induction of a L-type VDCC-dependent LTP in the CA1 region by application of the K+ channel blocker tetraethylammonium resulted in impaired LTP in TN-C mutants. Thus, reduction in L-type VDCC-mediated signaling appears to mediate the deficits in certain forms of synaptic plasticity in constitutively TN-C-deficient mice.

Original languageEnglish (US)
Pages (from-to)7177-7194
Number of pages18
JournalJournal of Neuroscience
Volume22
Issue number16
DOIs
StatePublished - Aug 15 2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • CA1
  • CA3
  • Dentate gyrus
  • Extracellular matrix glycoprotein
  • Gene targeting
  • Hippocampus
  • Knock-out mutation
  • L-type voltage-dependent Ca channels
  • Long-term depression
  • Long-term potentiation
  • Nifedipine
  • TEA
  • Tenascin-C
  • VDCC
  • Water maze

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