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

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 -