Effect Of αCaMKⅡ In The Lateral Amygdala On PTSD-like Symptoms In Mice

Post traumatic stress disorder（PTSD）is a chronic mental disease caused by extreme terrorist events,which has sustained and serious adverse effects on the body.However,for many years,there has been a lack of specifically therapeutic drugs or means for PTSD.The main symptoms of PTSD are the impairment of fear memory extinction and anxiety.Lateral amygdala（LA）is related to the regulation of fear and anxiety,whereby the mechanism of anxiety and memory impairment is still not clear.Studies have shown that the increase of αCa MKII causes anxiety.Does the change of αCa MKII in LA brain damage fear memory extinction,which leads to the PTSD-related phenotype? Therefore,through the profound study of the mechanism of LA Ca MKII in PTSD like symptoms,we want to seek the potential targets for PTSD related drugs.The results are as follows:1.The screening of PTSD susceptible mice and the expression of αCa MKII in LA on PTSD susceptible mice1)PTSD susceptible mice with impaired auditory fear extinction and significant anxiety were successfully constructed by SPS.2)The expression of LA αCa MKII and p-αCa MKII-Thr286 was significantly increased on PTSD susceptible mice.2.The up-regulated αCa MKII of forebrain leads to PTSD-like behavior and impairment of AMPA receptor internalization.1)The up-regulated αCa MKII of forebrain impaired fear extinction on αCa MKII-F89 G transgenic mice.2)The up-regulated αCa MKII of forebrain leads to significant anxiety on αCa MKII-F89 G transgenic mice.3)Suppressing the elevated αCa MKII by NM-PP1 could completely reverse the injury of auditory fear extinciton and anxiety on αCa MKII-F89 G transgenic mice.4)The up-regulated αCaMKII of forebrain deficits AMPAR internalization and GluA1-Ser845/Ser831 dephosphorylation on αCa MKII-F89 G transgenic mice during fear extinction.3.The specific up-regulation of LA αCa MKII leads to PTSD-like behavior and impairment of AMPA receptor internalization1)The specific up-regulation of LA αCa MKII impaired fear extinction on AAV-αCa MKII mice.2)The specific up-regulation of LA αCa MKII leads to significant anxiety on AAV-αCa MKII mice.3)The specific up-regulation of LA αCa MKII deficits AMPAR internalization and Glu A1-Ser845/Ser831 dephosphorylation on AAV-αCa MKII mice during fear extinction.In conclusion,our study has found that the expression of LA αCa MKII and AMPAR were significantly increased on PTSD susceptible mice.Increasing the expression of αCa MKII in forebrain or LA,can not only cause PTSD like symptoms,but also deficit AMPAR internalization and Glu A1-Ser845/Ser831 dephosphorylation during fear extinction.Therefore,our results confirm the relationship between the increase of LA αCa MKII and the fear memory extinction,suggesting that the increase of αCa MKII in LA may cause the PTSD-like phenotype.Our finding provides new implications for the clinical treatment of PTSD.