Rapid activity-dependent delivery of the neurotrophic protein CPG15 to the axon surface of neurons in intact Xenopus tadpoles

CPG15 (aka neuritin) is an activity-induced GPI-anchored axonal protein that promotes dendritic and axonal growth, and accelerates synaptic maturation in vivo. Here we show that CPG15 is distributed inside axons and on the axon surface. CPG15 is trafficked to and from the axonal surface by membrane depolarization. To assess CPG15 trafficking in vivo, we expressed an ecliptic pHluorin (EP)-CPG15 fusion protein in optic tectal explants and in retinal ganglion cells of intact Xenopus tadpoles. Depolarization by KCl increased EP-CPG15 fluorescence on axons. Intraocular kainic acid (KA) injection rapidly increased cell-surface EP-CPG15 in retinotectal axons, but coinjection of TTX and KA did not. Consistent with this, we find that intracellular CPG15 is localized to vesicles and endosomes in presynaptic terminals and colocalizes with synaptic vesicle proteins. The results indicate that the delivery of the neurotrophic protein CPG15 to the axon surface can be regulated on a rapid time scale by activity-dependent mechanisms in vivo. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol 2008

Kainic acid induction of mossy fiber sprouting. dependence on mouse strain

After seizures caused by kindling or kainic acid (KA), hippocampal granule-cell axons, the mossy fibers, sprout into the supragranular layer of the rat. The mechanisms underlying this phenomenon remain elusive, but excitotoxic loss of hilar cells, which project to this supragranular layer, is suspected to be a critical determinant. Consistent with this hypothesis, we previously reported that while rats show mossy fiber sprouting after kainate, ICR mice do not. This may be associated with the observation that ICR mice, unlike rats, do not appear to show hilar cell death after KA (McNamara et al., Mol Brain Res 1996;40:177-187), Other strains of mice, however, such as 129/SvEMS, do show hilar cell death after KA (Schauwecker and Steward, Proc Natl Acad Sci USA 1997;94:4103-4108). We examined the possibility that the 129/SvEMS mouse strain would show granule-cell sprouting, in contrast to ICR mice. After administration of KA, mossy fiber sprouting was indeed observed in strain 129/SvEMS, but only in animals displaying evident hilar cell death. In contrast, neither hilar cell death nor mossy fiber sprouting was observed in ICR mice, confirming previous results. Both mouse strains demonstrated comparable behavioral seizures. These results strengthen the view that hilar cell death, together with epileptogenesis, triggers reactive synaptogenesis and mossy fiber sprouting