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Impairment of L-type Ca2+Channel-Dependent Forms of Hippocampal Synaptic Plasticity in Mice Deficient in the Extracellular Matrix Glycoprotein Tenascin-C

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Evers, Matthias R., Salmen, Benedikt, Bukalo, Olena, Rollenhagen, Astrid, Bösl, Michael R., Morellini, Fabio, Bartsch, Udo, Dityatev, Alexander +1 more·2002·The Journal of Neuroscience

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.

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Crossref · 10.1523/jneurosci.22-16-07177.2002

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  1. Faissner A, Schachner M (1995) Tenascin and janusin: Glial recognition molecules involved in neural development and regeneration. In: Neu- roglia (Kettenmann H, Ransom BR, eds), pp 422-426. New York: Oxford University Press.

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Authors
Evers, M. R., Salmen, B., Bukalo, O., Rollenhagen, A., Bösl, M. R., Morellini, F., Bartsch, U., Dityatev, A., & Schachner, M.
Affiliations
Universität Hamburg (DE)
Venue
The Journal of Neuroscience
Published
2002-08-15
Volume
22
Issue
16
Pages
7177-7194
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2141616957
Cited by
172
References
81
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 6 · 2012: 10
FWCI
3.38
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Rutgers University Community Repository (Rutgers University) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Rheinische Friedrich-Wilhelms-Universität Bonn
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
tenascin-C, extracellular matrix, L-type calcium channels, hippocampal synaptic plasticity, long-term potentiation, long-term depression, CA1 region, dentate gyrus, Schaffer collaterals, perforant path, tetraethylammonium, nifedipine, floxed allele
MeSH terms
Animals, Behavior, Animal, Cerebellar Cortex, Electric Stimulation, Hippocampus, Male, Neural Inhibition, Neuronal Plasticity, Neurons, Optic Nerve, Retina, Synapses, Blotting, Western, Long-Term Potentiation, Mice, Knockout, Gene Targeting, Excitatory Amino Acid Antagonists, Maze Learning, Tenascin, Excitatory Postsynaptic Potentials, Calcium Channels, L-Type, Mice, In Vitro Techniques

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