title: Impaired presynaptic long-term potentiation in the anterior cingulate cortex of Fmr1 knock-out mice.
abstract: Fragile X syndrome is a common inherited form of mental impairment. Fragile X mental retardation protein (FMRP) plays important roles in the regulation of synaptic protein synthesis, and loss of FMRP leads to deficits in learning-related synaptic plasticity and behavioral disability. Previous studies mostly focus on postsynaptic long-term potentiation (LTP) in Fmr1 knock-out (KO) mice. Here, we investigate the role of FMRP in presynaptic LTP (pre-LTP) in the adult mouse anterior cingulate cortex (ACC). Low-frequency stimulation induced LTP in layer II/III pyramidal neurons under the voltage-clamp mode. Paired-pulse ratio, which is a parameter for presynaptic changes, was decreased after the low-frequency stimulation in Fmr1 wild-type (WT) mice. Cingulate pre-LTP was abolished in Fmr1 KO mice. We also used a 64-electrode array system for field EPSP recording and found that the combination of low-frequency stimulation paired with a GluK1-containing kainate receptor agonist induced NMDA receptor-independent and metabotropic glutamate receptor-dependent pre-LTP in the WT mice. This potentiation was blocked in Fmr1 KO mice. Biochemical experiments showed that Fmr1 KO mice displayed altered translocation of protein kinase A subunits in the ACC. Our results demonstrate that FMRP plays an important role in pre-LTP in the adult mouse ACC, and loss of this pre-LTP may explain some of the behavioral deficits in Fmr1 KO mice.
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China.
authors: Kohei
authors: K
authors: Koga
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Department of Anatomy and Histology and Embryology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China, and.
authors: Ming-Gang
authors: MG
authors: Liu
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China.
authors: Shuang
authors: S
authors: Qiu
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China.
authors: Qian
authors: Q
authors: Song
authors: Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China.
authors: Gerile
authors: G
authors: O'Den
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China, Department of Anatomy and KK Leung Brain Research Center, Fourth Military Medical University, Xi'an, Shanxi 710032, China.
authors: Tao
authors: T
authors: Chen
authors: Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, Toronto, Ontario, M5S 1A8, Canada, Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, China, min.zhuo@utoronto.ca.
authors: Min
authors: M
authors: Zhuo
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology; D018092:Kainic Acid Receptors / Q000819:agonists; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D051860:Fragile X Messenger Ribonucleoprotein 1; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C497684:Fmr1 protein, mouse
keywords: FMRP; LTP; PKA; cortex; fragile X disease; mice
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