Differential regulation of synaptic vesicle protein genes by target and synaptic activity

Differentiation of presynaptic nerve terminals involves changes in gene expression; these may be regulated by synaptic transmission and/or by contact with the target muscle. To gain insight into the control of presynaptic differentiation, we examined the regulation by target and synaptic activity of synaptic vesicle protein (SVP) genes in the chick ciliary ganglion (CG). In the CG, two SVP genes, synaptotagmin I (syt I) and synaptophysin II (syp II), are coordinately upregulated at the time of target contact. To test the hypothesis that this upregulation is induced by target contact, we examined mRNA levels of syt I and syp II in CGs from embryos in which one eye had been removed before axon outgrowth. As expected, target removal prevented the normal upregulation of syt I mRNA in the deprived ganglion. In contrast, and unexpectedly, syp II mRNA upregulation was not affected. The target dependence of syt I upregulation was not attributable to nerve-muscle transmission, because blockade of this transmission had no effect on SVP mRNA levels. Surprisingly, blockade of synapses onto CG neurons from the brain also did not affect syt I mRNA levels but increased levels of syp II mRNA. We conclude that contact with target induces upregulation of syt I mRNA, which is the case for spinal motor neurons. However, the normal upregulation of syp II mRNA is not controlled by the same signal(s). Instead, our results suggest that these two SVP genes are differentially regulated, both by target contact and by blockade of synaptic transmission.