title: Learning-Induced Suboptimal Compensation for PKCι/λ Function in Mutant Mice.
abstract: PKCι/λ has been proposed to be crucial in the early expression of long-term potentiation (LTP). Here, we further investigate the potential role of PKCι/λ in learning and memory by generating PKCι/λ conditional knockout mice specifically lacking PKCι/λ in the hippocampal CA1 pyramidal cells. Surprisingly, PKCι/λ cKO mice show normal hippocampal LTP and memory. Further close-up observation reveals compensation for PKCι/λ expression by PKMζ in PKCι/λ cKO mice. This compensation was not observed under basal conditions, but was detected either after LTP induction or learning-associated behavioral training. Accordingly, in the early stage of LTP expression, a switch from PKCι/λ- to PKMζ-dependent molecular mechanisms was detected in PKCι/λ cKO mice. Notably, when cKO mice were challenged with more difficult hippocampus-dependent learning tasks, moderate learning deficits were detected, suggesting a suboptimal compensation for PKCι/λ's function in PKCι/λ cKO mice. Thus, under physiological conditions, PKCι/λ is essential for hippocampal early-LTP and long-term memory (LTM).
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing 210096, Jiangsu Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sheng
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing 210096, Jiangsu Province, China.
authors.forename: Shaoli
authors.initials: S
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing 210096, Jiangsu Province, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.|State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center and MOE Key Laboratory of Model Animal for Disease Study Nanjing University, Nanjing 210032, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.affiliation: MOE Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing 210096, Jiangsu Province, China.|Department of Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003213:Conditioning, Psychological; D004558:Electric Stimulation; D005239:Fear; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D008297:Male; D018782:Maze Learning; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000099221:Protein Kinase C zeta
chemical_list: D011493:Protein Kinase C; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D000099221:Protein Kinase C zeta
keywords: LTP; PKCι/λ; PKMζ; compensation; learning and memory