Establishment Of A Mouse Model Of Post-traumatic Stress Disorder And Study Of Its Potential Mechanism

Post-traumatic stress disorder(PTSD)is a chronic and persistent mental disorder caused by acute severe stress events,often accompanied by symptoms such as depression and anxiety-like disorder.A large number of studies have shown that single prolonged stress(SPS)or footshock stress(FS)can significantly induce PTSD-like behavior in rats and is widely used in understanding the pathogenesis of rat PTSD.However,as the most commonly used animal model,whether the above stress model can effectively induce PTSD-like behavior in mice is not clearly understood.To this end,we first established mice PTSD model by using a variety of acute stress models.To evaluate the efficiency of PTSD model,the anxiety-like behavior of PTSD mice was measured 7 or 14 days after stress by open field and elevated plus maze test,and the expression of BDNF was detected by molecular biology method.The results showed that SPS had no significant effect on the anxiety-like behavior in mice,while FS with current intensity of 0.3 m A or 0.5 m A only had a slight effect on the anxiety-like behavior of mice 7 days at the end of stress,and completely recoverd to the normal level after 14 days.In contrast,FS mice with 0.5 m A for two consecutive days(hereafter refered to as FS)showed significant anxiety-like behavior at 7 and 14 days at the end of stress.Further studies showed that FS significantly decreased the expression of BDNF protein and m RNA transcription in the hippocampus,which indicates that FS can effectively induce PTSD-like behavior in mice.We subsequently used this model to explore its potential neurobiological mechanisms.The results showed that FS significantly increased the frequency but not amplitude of miniature excitatory postsynaptic currents(m EPSCs)of BLA neurons projected to ventral hippocampus(BLA→v HPC),suggesting glutamate released from presynapse was increased on BLA→v HPC neurons.On the contrary,no obvious effect was observed on those projected to nucleus accumbens(BLA→NAc).Thus,we established a single neuron capture technique and successfully captured single neuron of these two neuron populations.By establishing a single-cell c DNA library based on SMART-seq2 technology,our q PCR results showed that FS had no obvious effect on the m RNA level of m Glu R5,which palys an important in regulating neurotransmitter release at presynapse,in both types of projection neurons.In conclusion,we successfully established an effective mice model of PTSD.Based on this model,the effects of FS on the electrophysiological function of different types of projection neurons in the amygdala were preliminarily studied from the neural circuit level,which may provide some theoretical basis for understanding the neurobiological mechanism of PTSD...