title: Overexpression of Protein Kinase Mζ in the Prelimbic Cortex Enhances the Formation of Long-Term Fear Memory.
abstract: Neuroplasticity in the prefrontal cortex (PFC) after fear conditioning has been suggested to regulate the formation and expression of fear memory. Protein kinase Mζ (PKMζ), 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 PKMζ in the PFC in the formation of fear memory. We investigated whether the overexpression of PKMζ enhances the formation of auditory fear memory in rats. We found that microinfusion of lentiviral vector-expressing PKMζ into the prelimbic cortex (PrL) selectively enhanced the expression of PKMζ without influencing the expression of other isoforms of PKC. The overexpression of PKMζ in the PrL enhanced the formation of long-term fear memory without affecting short-term fear memory, whereas the overexpression of PKMζ in the infralimbic cortex had no effect on either short-term or long-term fear memory. The overexpression of PKMζ in the PrL had no effect on anxiety-like behavior or locomotor activity. We also found that PKMζ 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 PKMζ in the PrL but not infralimbic cortex selectively enhanced the formation of long-term fear memory, and PKMζ in the PrL may be involved in the formation of fear memory.
authors.affiliation: National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.
authors.forename: Yan-Xue
authors.initials: YX
authors.lastname: Xue
authors.affiliation: 1] Tianjin Medical University, Tianjin, China [2] Center of Tianjin Mental Health Center, Tianjin, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Zhu
authors.affiliation: 1] Tianjin Medical University, Tianjin, China [2] Center of Tianjin Mental Health Center, Tianjin, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Han
authors.affiliation: 1] National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China [2] Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Beijing, China [3] Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Liu
authors.affiliation: 1] National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China [2] Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Beijing, China [3] Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Shi-Qiu
authors.initials: SQ
authors.lastname: Meng
authors.affiliation: 1] National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China [2] Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Beijing, China [3] Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: 1] Tianjin Medical University, Tianjin, China [2] Center of Tianjin Mental Health Center, Tianjin, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Yang
authors.affiliation: National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: 1] National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China [2] Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Beijing, China [3] Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D009043:Motor Activity; D017397:Prefrontal Cortex / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat