| First Author | Horn KE | Year | 2012 |
| Journal | J Neurochem | Volume | 122 |
| Issue | 1 | Pages | 147-61 |
| PubMed ID | 22519304 | Mgi Jnum | J:186269 |
| Mgi Id | MGI:5431284 | Doi | 10.1111/j.1471-4159.2012.07762.x |
| Citation | Horn KE, et al. (2012) Receptor protein tyrosine phosphatase sigma regulates synapse structure, function and plasticity. J Neurochem 122(1):147-61 |
| abstractText | 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 sigma (RPTPsigma), 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 RPTPsigma function in the mature brain. We demonstrate increased axon collateral branching in the hippocampus of RPTPsigma null mice during normal aging or following chemically induced seizure, indicating that RPTPsigma maintains neural circuitry by inhibiting axonal branching. Previous studies demonstrated a role for pre-synaptic RPTPsigma promoting synaptic differentiation during development; however, subcellular fractionation revealed enrichment of RPTPsigma in post-synaptic densities. We report that neurons lacking RPTPsigma have an increased density of pre-synaptic varicosities in vitro and increased dendritic spine density and length in vivo. RPTPsigma 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, RPTPsigma nulls exhibit reduced long-term potentiation and enhanced novel object recognition memory. We conclude that RPTPsigma limits synapse number and regulates synapse structure and function in the mature CNS. |
