Overexpression of Protein Kinase M ζ in the Prelimbic Cortex Enhances the Formation of Long-Term fear Memory

【作者】 朱珍珍； 张庆玉； 胡珍玉； 禹海航； 陆林； 杨建立； 阮列敏；

【Author】 Zhen-Zhen Zhu;Qing-Yu Zhang;Zhen-Yu Hu;Hai-Hang Yu;Lin Lu;Jian-Li Yang;Lie-Min Ruan;Institute of Mental Health,Ningbo KangNing Hospital;Institute of Mental Health,Ningbo First Hospital;Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health;Center of Tianjin Mental Health Center;

【机构】 Institute of Mental Health,Ningbo KangNing Hospital； Institute of Mental Health,Ningbo First Hospital； Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health； Center of Tianjin Mental Health Center；

【摘要】 Neuroplasticity in the prefrontal cortex(PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory.Protein kinase M ζ(PKM ζ),an isoform of protein kinase C with persistent activity,is involved in the formation and maintenance of memory.However,less is known about the role of PKM ζ in the PFC in the formation of fear memory.We investigated whether the overexpression of PKM ζ enhances the formation of auditory fear memory in rats.We found that microinfusion of lentiviral vectorexpressing PKM ζ into the prelimbic cortex(PrL) selectively enhanced the expression of PKM ζ without influencing the expression of other isoforms of PKC.The overexpression of PKM ζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory,whereas the overexpression of PKM ζ in the infralimbic cortex had no effect on either shortterm or long-term fear memory.The overexpression of PKM ζ in the PrL had no effect on anxiety-like behavior or locomotor activity.We also found that PKM ζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL.These results demonstrate that the overexpression of PKM ζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory,and PKM ζ in the PrL may be involved in the formation of fear memory.更多还原

【Abstract】 Neuroplasticity in the prefrontal cortex(PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory.Protein kinase M ζ(PKM ζ),an isoform of protein kinase C with persistent activity,is involved in the formation and maintenance of memory.However,less is known about the role of PKM ζ in the PFC in the formation of fear memory.We investigated whether the overexpression of PKM ζ enhances the formation of auditory fear memory in rats.We found that microinfusion of lentiviral vectorexpressing PKM ζ into the prelimbic cortex(PrL) selectively enhanced the expression of PKM ζ without influencing the expression of other isoforms of PKC.The overexpression of PKM ζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory,whereas the overexpression of PKM ζ in the infralimbic cortex had no effect on either shortterm or long-term fear memory.The overexpression of PKM ζ in the PrL had no effect on anxiety-like behavior or locomotor activity.We also found that PKM ζ overexpression potentiated the fear conditioning-induced increase in the membrane levels of glutamate subunit 2 of AMPA receptors in the PrL.These results demonstrate that the overexpression of PKM ζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory,and PKM ζ in the PrL may be involved in the formation of fear memory.更多还原