海马新生神经元与抑郁病理/抗抑郁治疗关系极为密切，但抑郁症海马新生神经元环路构建情况，特别是其具体哪条神经环路构建紊乱/重塑与抑郁/抗抑郁行为产生有关迄今未明。我们预实验研究发现沿海马Dorsal-Ventral Axis（腹背轴）分布的成年新生神经元的输入/输出神经环路构建模式具有显著异质性。更重要是，我们发现氟西汀和慢性应激选择性共同重塑内嗅皮层尾内侧-海马中间区新生神经元环路构建。基于预实验结果和我们发展的新技术，本项目拟运用基于病毒的跨突触追踪神经环路方法，阐明沿海马腹背轴分布的新生神经元神经环路在抑郁模型和抗抑郁药物干预下的构建规律；并拟融合化学遗传学和转基因小鼠发展一种激活/抑制特定神经环路技术，解析鉴定内嗅皮层尾内侧谷氨酸能神经元-海马中间侧新生神经元环路构建在抑郁/抗抑郁中行为产生中作用；运用qPCR、基因芯片、WB、Clonging、蛋白芯片等技术阐明与其相关的分子机制。

Hippocampal newborn neurons (HNN) are critically involved in the pathology of depression and the effect of antidepressants. However, how the circuit of HNN establish, especially, and which circuit of them account for the generation of depressive/antidepressive behavior remains unknown. Our preliminary experiment revealed significant heterogeneous connectivity patterns of HNN along the dorsal-ventral axis of the hippocampus. More importantly, we found that fluoxetine treatment and chronic stress selectively remodeled the input circuit of HNN located in the intermediate region from caudomedial entorhinal cortex. Accordingly, we plan to apply a viral trans-synaptic tracing tool to study how depression and antidepressant affect the circuit formation of HNN along the dorsal-ventral axis. Moreover, we plan to develop an activation/inhibition of certain neural circuit based Dreadds and Cre transgenic mice to identify the role of glutamatergic neuron in the caudomedial entorhinal cortex-newborn neuron in the intermediate hippocampus circuit in the generation of depressive/antidepressive behaivor Next, we plan to use qPCR, gene assay, Cloning, protein assay, and Western blot to clarify the molecular mechanism.