Fibronectin domains of extracellular matrix molecule tenascin-C modulate hippocampal learning and synaptic plasticity.
The extracellular matrix molecule tenascin-C (TN-C) has been shown to be involved in hippocampal synaptic plasticity in vitro. Here, we describe a deficit in hippocampus-dependent contextual memory in TN-C-deficient mice using the step-down avoidance paradigm. We further show that a fragment of TN-C containing the fibronectin type-III repeats 6-8 (FN6-8), but not a fragment containing repeats 3-5, bound to pyramidal and granule cell somata in the hippocampal formation of C57BL/6J mice and repelled axons of pyramidal neurons when presented as a border in vitro. Injection of the FN6-8 fragment into the hippocampus inhibited retention of memory in the step-down paradigm and reduced levels of long-term potentiation in the CA1 region of the hippocampus. In summary, our data show that TN-C is involved in hippocampus-dependent contextual memory and synaptic plasticity and identify the FN6-8 domain as one of molecular determinants mediating these functions.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D019063:Tenascin / Q000172:deficiency* / Q000235:genetics
D005353:Fibronectins; D010446:Peptide Fragments; D019063:Tenascin