Tissue Engineering and Regenerative Medicine

Neurogenesis in the sub-ventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Although the regulation of neurogenesis by molecular genes and signal pathways has been extensively investigated, especially in the dentate gyrus (DG) of the hippocampus, whether SVZ neurogenesis can be regulated by neuronal activities is not well defined. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we showed morphological and functional evidence of a novel neuronal link between the striatum and SVZ. Transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release that consequently evoked membrane currents, Ca2+ influx and increased proliferation of SVZ neural stem cells, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum not only promoted cell proliferation but also the migration of neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ connection that up-regulates SVZ neurogenesis and may be a therapeutic target for promoting adult neurogenesis and brain tissue repair.