Syndecan-3-deficient mice exhibit enhanced LTP and impaired hippocampus-dependent memory.
Syndecan-3 (N-syndecan) is a transmembrane heparan sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated manner. Syndecan-3 has been suggested to play a role in the development and plasticity of neuronal connections by linking extracellular signals to the regulation of the cytoskeleton. To study its physiological functions, we produced mice deficient in syndecan-3 by gene targeting. The mutant animals are healthy, are fertile, and have no apparent defects in the structure of the brain. We focused on characterizing the functions of the hippocampus, a brain area where expression of syndecan-3 is prominent in adults. Mice lacking syndecan-3 exhibited an enhanced level of long-term potentiation (LTP) in area CA1, while basal synaptic transmission and short-term plasticity were similar to those in wild-type animals. Further, the mutant mice were not responsive to the syndecan-3 ligand heparin-binding growth-associated molecule, which inhibits LTP in area CA1 in wild-type animals. Behavioral testing of the syndecan-3-deficient mice revealed impaired performance in tasks assessing hippocampal functioning. We suggest that syndecan-3 acts as an important modulator of synaptic plasticity that influences hippocampus-dependent memory.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D053670:Syndecan-3
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011994:Recombinant Proteins; C508302:Sdc3 protein, mouse; D053670:Syndecan-3; C066845:pleiotrophin