Receptor protein tyrosine phosphatase sigma regulates synapse structure, function and plasticity

J. Neurochem. (2012) 122, 147161. 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 s (RPTPs), 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 RPTPs function in the mature brain. We demonstrate increased axon collateral branching in the hippocampus of RPTPs null mice during normal aging or following chemically induced seizure, indicating that RPTPs maintains neural circuitry by inhibiting axonal branching. Previous studies demonstrated a role for pre-synaptic RPTPs promoting synaptic differentiation during development; however, subcellular fractionation revealed enrichment of RPTPs in post-synaptic densities. We report that neurons lacking RPTPs have an increased density of pre-synaptic varicosities in vitro and increased dendritic spine density and length in vivo. RPTPs 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, RPTPs nulls exhibit reduced long-term potentiation and enhanced novel object recognition memory. We conclude that RPTPs limits synapse number and regulates synapse structure and function in the mature CNS.