Receptor protein tyrosine phosphatase sigma regulates synapse structure, function and plasticity.
J Neurochem
; 122(1): 147-61, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22519304
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Potenciação de Longa Duração
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Regulação da Expressão Gênica no Desenvolvimento
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Reconhecimento Psicológico
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Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores
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Densidade Pós-Sináptica
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá