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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Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C. / Evers, Matthias R; Salmen, Benedikt; Bukalo, Olena; Rollenhagen, Astrid; Bösl, Michael R; Morellini, Fabio; Bartsch, Udo; Dityatev, Alexander; Schachner, Melitta.
In: J NEUROSCI, Vol. 22, No. 16, 15.08.2002, p. 7177-94.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C
AU - Evers, Matthias R
AU - Salmen, Benedikt
AU - Bukalo, Olena
AU - Rollenhagen, Astrid
AU - Bösl, Michael R
AU - Morellini, Fabio
AU - Bartsch, Udo
AU - Dityatev, Alexander
AU - Schachner, Melitta
PY - 2002/8/15
Y1 - 2002/8/15
N2 - 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.
AB - 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.
KW - Animals
KW - Behavior, Animal
KW - Blotting, Western
KW - Calcium Channels, L-Type
KW - Cerebellar Cortex
KW - Electric Stimulation
KW - Excitatory Amino Acid Antagonists
KW - Excitatory Postsynaptic Potentials
KW - Gene Targeting
KW - Hippocampus
KW - In Vitro Techniques
KW - Long-Term Potentiation
KW - Male
KW - Maze Learning
KW - Mice
KW - Mice, Knockout
KW - Neural Inhibition
KW - Neuronal Plasticity
KW - Neurons
KW - Optic Nerve
KW - Retina
KW - Synapses
KW - Tenascin
U2 - 20026735
DO - 20026735
M3 - SCORING: Journal article
C2 - 12177213
VL - 22
SP - 7177
EP - 7194
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 16
ER -