title: Receptor protein tyrosine phosphatase sigma regulates synapse structure, function and plasticity.
abstract: The mechanisms that regulate synapse formation and maintenance are incompletely understood. In particular, relatively few inhibitors of synapse formation have been identified. Receptor protein tyrosine phosphatase σ (RPTPσ), a transmembrane tyrosine phosphatase, is widely expressed by neurons in developing and mature mammalian brain, and functions as a receptor for chondroitin sulfate proteoglycans that inhibits axon regeneration following injury. In this study, we address RPTPσ function in the mature brain. We demonstrate increased axon collateral branching in the hippocampus of RPTPσ null mice during normal aging or following chemically induced seizure, indicating that RPTPσ maintains neural circuitry by inhibiting axonal branching. Previous studies demonstrated a role for pre-synaptic RPTPσ promoting synaptic differentiation during development; however, subcellular fractionation revealed enrichment of RPTPσ in post-synaptic densities. We report that neurons lacking RPTPσ have an increased density of pre-synaptic varicosities in vitro and increased dendritic spine density and length in vivo. RPTPσ knockouts exhibit an increased frequency of miniature excitatory post-synaptic currents, and greater paired-pulse facilitation, consistent with increased synapse density but reduced synaptic efficiency. Furthermore, RPTPσ nulls exhibit reduced long-term potentiation and enhanced novel object recognition memory. We conclude that RPTPσ limits synapse number and regulates synapse structure and function in the mature CNS.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Horn
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Delphine
authors.initials: D
authors.lastname: Gobert
authors.forename: Bassam N
authors.initials: BN
authors.lastname: Hamam
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Thompson
authors.forename: Chia-Lun
authors.initials: CL
authors.lastname: Wu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bouchard
authors.forename: Noriko
authors.initials: N
authors.lastname: Uetani
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Racine
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
authors.forename: Edward S
authors.initials: ES
authors.lastname: Ruthazer
authors.forename: C Andrew
authors.initials: CA
authors.lastname: Chapman
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Kennedy
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007608:Kainic Acid / Q000633:toxicity; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009483:Neuropsychological Tests; D018408:Patch-Clamp Techniques; D057907:Post-Synaptic Density / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000172:deficiency / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D016622:Silver Staining; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000473:pathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D007608:Kainic Acid