title: Pharmacological rescue of cortical synaptic and network potentiation in a mouse model for fragile X syndrome.
abstract: Fragile X syndrome, caused by the mutation of the Fmr1 gene, is characterized by deficits of attention and learning ability. In the hippocampus of Fmr1 knockout mice (KO), long-term depression is enhanced whereas long-term potentiation (LTP) including late-phase LTP (L-LTP) is reduced or unaffected. Here we examined L-LTP in the anterior cingulate cortex (ACC) in Fmr1 KO mice by using a 64-electrode array recording system. In wild-type mice, theta-burst stimulation induced L-LTP that does not occur in all active electrodes/channels within the cingulate circuit and is typically detected in ∼75% of active channels. Furthermore, L-LTP recruited new responses from previous inactive channels. Both L-LTP and the recruitment of inactive responses were blocked in the ACC slices of Fmr1 KO mice. Bath application of metabotropic glutamate receptor 5 (mGluR5) antagonist or glycogen synthase kinase-3 (GSK3) inhibitors rescued the L-LTP and network recruitment. Our results demonstrate that loss of FMRP will greatly impair L-LTP and recruitment of cortical network in the ACC that can be rescued by pharmacological inhibition of mGluR5 or GSK3. This study is the first report of the network properties of L-LTP in the ACC, and provides basic mechanisms for future treatment of cortex-related cognitive defects in fragile X patients.
authors.affiliation: 1] Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China [2] Department of Anatomy and KK Leung Brain Research Center, Fourth Military Medical University, Xi'an, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Lu
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Song
authors.affiliation: 1] Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China [2] Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Ming-Gang
authors.initials: MG
authors.lastname: Liu
authors.affiliation: 1] Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China [2] Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Giannina
authors.initials: G
authors.lastname: Descalzi
authors.affiliation: Department of Anatomy and KK Leung Brain Research Center, Fourth Military Medical University, Xi'an, China.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
authors.affiliation: 1] Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China [2] Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000503:physiopathology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000503:physiopathology*; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D038362:Glycogen Synthase Kinase 3; D064529:Receptor, Metabotropic Glutamate 5; C497684:Fmr1 protein, mouse