title: Conditional deletion of Eps8 reduces hippocampal synaptic plasticity and impairs cognitive function.
abstract: Epidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein involved in actin cytoskeleton regulation and is abundantly expressed in many brain regions. However, the functional significance of Eps8 in the brain has only just begun to be elucidated. Here, we demonstrate that genetic deletion of Eps8 (Eps8-/-) from excitatory neurons leads to impaired performance in a novel object recognition test. Consistently, Eps8-/-mice displayed a deficit in the maintenance of long-term potentiation in the CA1 region of hippocampal slices, which was rescued by bath application of N-methyl-d-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonopentanoate. While Eps8-/-mice showed normal basal synaptic transmission, a significant increase in the amplitude and a significantly slower decay kinetic of NMDAR-mediated excitatory postsynaptic currents (EPSCs) were observed in hippocampal CA1 neurons. Furthermore, a significant increase in the expression of ifenprodil-sensitive NMDAR-mediated EPSCs was observed in neurons from Eps8-/-mice compared with those from wild-type mice. Eps8 deletion led to decreased mature mushroom-shaped dendritic spine density but increased complexity of basal dendritic trees of hippocampal CA1 pyramidal neurons. These results implicate NMDAR hyperfunction in the cognitive deficits observed in Eps8-/-mice and demonstrate a novel role for Eps8 in regulating hippocampal long-term synaptic plasticity and cognitive function. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Yun-Shan
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Weu-Fang
authors.initials: WF
authors.lastname: Huang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Cheng-Che
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Yeh
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan. Electronic address: richard@mail.ncku.edu.tw.
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D017353:Gene Deletion; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D008559:Memantine; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D013569:Synapses / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008559:Memantine; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C083430:Eps8 protein, mouse; C121673:Gprin1 protein, mouse; C121001:NR2B NMDA receptor
keywords: Cognition; Eps8; Hippocampus; Long-term potentiation; NMDA receptor