抑郁症发病率、复发率和自杀率高，最新研究表明与突触可塑性异常有关。近年发现氯胺酮等多种快速型抗抑郁症制剂能快速高效缓解抑郁症，可能都与快速增强突触可塑性有关，但启动机制不明。推测不同制剂可能通过不同途径快速启动胞内钙浓度增高、促使AMPA受体trafficking、增强突触可塑性而起作用。为证此假设，本项目使用包括先进的双光子显微镜活体阴影膜片钳、双光子解笼锁标测受体及解笼锁诱发LTP等技术，动态观察氯胺酮、GLYX-13和2R,6R-HNK对慢性不可预知应激（CUS）模型小鼠抑郁状态、CUS小鼠情感区神经元树突和树突棘形态、钙信号、AMPA受体trafficking和突触可塑性的影响；观察NMDA受体阻滞剂AP5、电压门控钙通道阻滞剂Nifedipine和胞库钙释放阻滞剂CPA是否消除上述制剂对上述指标的改善作用，阐明不同快速型抗抑郁症制剂快速启动治疗抑郁症途径，为抑郁症的防治提供依据。

Depression is a mental illness with high rates of incidence, relapse and suicide. The latest researches show that its pathogenesis is related to abnormal synaptic plasticity. In recent years, it has been found that various types of antidepressants, such as ketamine, can rapidly and efficiently relieve depression by possible rapid potentiation of synaptic plasticity, but the mechanism of rapid onset of the action is unknown. We speculate that the rapid increase of intracellular calcium concentration by different antidepressants in various ways initiates trafficking of AMPA receptor and potentiation of synaptic plasticity. To prove this hypothesis, several advanced techniques including in vivo shadow patch with two-photon microscopy, two-photon uncage mapping receptors and LTP induced by two-photon uncage will be used to observe the effects of ketamine, GLYX-13 and (2R, 6R)-HNK on the depressive behavior of the mice with chronic unpredictable stress (CUS) model, the morphological structure of dendrites and dendritic spines, calcium signal, trafficking of AMPA receptor and synaptic plasticity of the neurons from pre-frontal cortex (PFC) and hippocampus in CUS mice; and to observe if AP5, a NMDA receptor antagonist, Nifedipine, a voltage-gated calcium channel blockers and CPA, a inhibitor of calcium releasing from calcium store can respectively eliminate above relief effects of ketamine, GLYX-13 or (2R, 6R)-HNK on CUS mice. The research findings will potentially lead to clarify different rapidly initiatating pathways of the depressive treatment by various types of antidepressants, and to provide the theoretical evidance for the prevention and treatment of depression.