title: Developmental regulation of hippocampal long-term depression by cofilin-mediated actin reorganization.
abstract: Long lasting synaptic plasticity involves both functional and morphological changes, but how these processes are molecularly linked to achieve coordinated plasticity remains poorly understood. Cofilin is a common target of multiple signaling pathways at the synapse and is required for both functional and spine plasticity, but how it is regulated is unclear. In this study, we investigate whether the involvement of cofilin in plasticity is developmentally regulated by examining the role of cofilin in hippocampal long-term depression (LTD) in both young (2 weeks) and mature (2 months) mice. We show that both total protein level of cofilin and its activation undergo significant changes as the brain matures, so that although the amount of cofilin decreases significantly in mature mice, its regulation by protein phosphorylation becomes increasingly important. Consistent with these biochemical data, we show that cofilin-mediated actin reorganization is essential for LTD in mature, but not in young mice. In contrast to cofilin, the GluA2 interactions with NSF and PICK1 appear to be required in both young and mature mice, indicating that AMPAR internalization is a common key mechanism for LTD expression regardless of the developmental stages. These results establish the temporal specificity of cofilin in LTD regulation and suggest that cofilin-mediated actin reorganization may serve as a key mechanism underlying developmental regulation of synaptic and spine plasticity. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Canada; The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.affiliation: Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada; The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China; Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China.
authors.forename: Zikai
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China.
authors.forename: Xingxiu
authors.initials: X
authors.lastname: Pan
authors.affiliation: Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Canada.
authors.forename: Celeste
authors.initials: C
authors.lastname: Leung
authors.affiliation: The Key Laboratory of Developmental Genes and Human Disease, Jiangsu Co-innovation Center of Neuroregeneration, Southeast University, Nanjing 210096, China; Institute of Life Sciences, The Collaborative Innovation Center for Brain Science, Southeast University, Nanjing 210096, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Canada; Centre for Synaptic Plasticity, School of Physiology & Pharmacology, University of Bristol, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Collingridge
authors.affiliation: Neurosciences & Mental Health, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Canada. Electronic address: zhengping.jia@sickkids.ca.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism / Q000502:physiology*; D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D036881:Long-Term Synaptic Depression; D051379:Mice; D008810:Mice, Inbred C57BL; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse
keywords: AMPA receptor; Actin; Cofilin; Developmental regulation; Hippocampal LTD; NSF; PICK1