Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex

Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras ([H-ras.sup.G12V]), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, [H-ras.sup.G12V] not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, [H-ras.sup.G12v] expression decreased baseline presynaptic release probability and enhanced presynaptically expressed longterm potentiation (LTP). [H-ras.sup.G12v] expression also accelerated the increase following M D in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders. gain of function | monocular deprivation | mouse | ocular dominance | presynaptic long-term potentiation doi/ 10.1073/pnas.1013866107