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

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.

Conditional Ablation of the Neural Cell Adhesion Molecule Reduces Precision of Spatial Learning, Long-Term Potentiation, and Depression in the CA1 Subfield of Mouse Hippocampus

“…HFS performed in the presence of AP-5 induced a strong increase in fEPSP amplitudes (Fig. 7C,D), resembling reported profiles of CA3 LTP in mice (Eckhardt et al, 2000;Contractor et al, 2001;Evers et al, 2002;Dietrich et al, 2003). Post-tetanic potentiation (PTP) during the first 1 min after HFS was ϳ900% above the baseline in both genotypes, and mean potentiation measured 50 -60 min after induction of LTP was 62.8 Ϯ 17.8% in NCAMffϪ and 74.8 Ϯ 19.1% in NCAMffϩ mice ( p Ͼ 0.6) (Fig.…”

Interactions with PDZ Proteins Are Required for L-Type Calcium Channels to Activate cAMP Response Element-Binding Protein-Dependent Gene Expression

“…For example, calcium entry through L-type calcium channels activates NFATc4, whereas calcium through NMDA receptors will not (Graef et al, 1999). Recently, L-type calcium channel-mediated, but not NMDA receptor-mediated, long-term potentiation and long-term depression were altered after disruption of the gene encoding extracellular matrix glycoprotein tenascin-C (Evers et al, 2002). These data further suggest that activation of L-type calcium channels and NMDA receptors lead to distinct aspects of plasticity.…”

Amyloid precursor protein and amyloid β-peptide bind to ATP synthase and regulate its activity at the surface of neural cells

“…Hippocampal slice preparation and recordings of long-term potentiation (LTP) at CA3-CA1 synapses were performed as described elsewhere. 38,39 Briefly, after CO 2 anesthesia, decapitation and removal of the brain, the hippocampi were cut with a vibratome in 350 mm thick slices in ice-cold artificial cerebrospinal fluid (ACSF) containing: 250 mM sucrose, 25 mM NaHCO 3 , 25 mM glucose, 2.5 mM KCl, 1.25 mM NaH 2 -PO 4 , 2 mM CaCl 2 and 1.5 mM MgCl 2 (pH 7.3). The slices were then kept at RT in a chamber filled with carbogen-bubbled ACSF, containing 125 mM NaCl instead of 250 mM sucrose, for at least 2 h before the start of recordings.…”