卒中后抑郁(PSD)是一种常见的脑卒中后复杂神经精神疾病，严重影响预后，缺乏有效治疗。PSD发病机制与前额叶皮层下回路破坏，突触可塑性、谷氨酸递质改变等有关，但具体机制不明。我们前期发现：死亡相关蛋白激酶1（DAPK1）及下游信号介导卒中后神经元死亡，敲除DAPK1基因或阻断其信号，可减轻脑缺血损伤并缓解PSD。此外，PSD小鼠背侧海马（dCA1）到内侧前额叶皮层（mPFC）投射纤维丢失。本项目拟在此基础上，运用转基因小鼠建立PSD模型，结合病毒示踪、光遗传学、电生理以及抑郁样行为学检测方法，探究：（1）dCA1-mPFC神经突触DAPK1及其下游分子信号；（2）dCA1-mPFC突触结构与突触传递功能；（3）dCA1-mPFC神经环路与抑郁样行为的关系。本研究将揭示卒中后DAPK1信号通过损伤突触进而损伤dCA1-mPFC环路介导PSD的分子神经环路机制，为PSD的临床治疗提供新策略。

Post-stroke depression (PSD) is a common and complex post-stroke neuropsychiatric disorder, which not only delays functional recovery but also increases mortality, and currently lacks effective drug therapy. The pathogenesis of PSD is associated with impairment of the subcortical circuits of the prefrontal cortex, and alterations of synaptic plasticity, glutamate neurotransmitter and so on, but the exact mechanisms of PSD is still unknown. Our previous work indicates that the death associated protein kinase 1 (DAPK1) mediates neuronal death after stroke. Knockout DAPK1 gene or blocking of DAPK1 signal in PSD mouse model can not only alleviate cerebral ischemic injury, but also relieve post-stroke depression like behaviors. Based on the previous work, by using genetically modified mice to establish PSD model, combined with neural tracing, optogenetics, electric physiology and depression like behavior detection methods, the present study is proposed to investigate: (1)DAPK1 signal in the synapse of dCA1-mPFC neural circuits, (2) the structure and functions of dCA1-mPFC neural circuits after stroke, and (3) their relations with post-stroke depression like behaviors. Our study will further replenish the molecular and neural circuits mechanisms involved in post-stroke depression and provide new insights for the treatment of PSD.