Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day). The expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors, and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors, and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, are mediated by insulin increase in the dentate gyrus and subsequently activation of its downstream signaling pathway.

海马齿状回的成人神经发生在学习和记忆中起关键作用。源自内嗅皮层的投射，称为穿孔通路，为齿状回提供主要输入并促进神经发生。然而，尚未完全了解介导该途径的神经源性影响的神经调节剂和分子变化。在这里，通过光遗传学方法，我们研究了通过刺激穿孔通路诱导的成年大鼠海马的神经发生和突触可塑性。将携带受 CaMKII 启动子控制的 hChR2 (H134R)-mCherry 基因的慢病毒注射到成年大鼠的内侧内嗅皮层区域。21 天后，内嗅皮层区域连续 5 天（30 分钟/天）暴露于蓝色激光 (473 nm)。使用分子和组织学方法评估海马突触可塑性和神经发生标志物的表达。同时，评估了胰岛素及其信号通路、营养因子和线粒体生物发生成分的基因表达变化。我们的研究结果表明，内嗅皮层的光遗传学刺激可促进海马神经发生和突触可塑性，同时增加胰岛素 mRNA 及其信号标志物、神经营养因子和线粒体生物发生的水平。这些发现表明，穿孔通路刺激对海马体的影响，至少部分是由齿状回中的胰岛素增加和随后激活其下游信号通路介导的。