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      Regulation of neural process growth, elaboration and structural plasticity by NF-κB

      review-article
        * ,
      Trends in Neurosciences
      Elsevier Applied Science Publishing

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          Abstract

          The nuclear factor-kappa B (NF-κB) family of transcription factors has recently emerged as a major regulator of the growth and elaboration of neural processes. NF-κB signaling has been implicated in controlling axon initiation, elongation, guidance and branching and in regulating dendrite arbor size and complexity during development and dendritic spine density in the adult. NF-κB is activated by a variety of extracellular signals, and either promotes or inhibits growth depending on the phosphorylation status of the p65 NF-κB subunit. These novel roles for NF-κB, together with recent evidence implicating NF-κB in the regulation of neurogenesis in the embryo and adult, have important implications for neural development and for learning and memory in the mature nervous system.

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          Most cited references71

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          Structural dynamics of dendritic spines in memory and cognition.

          Recent studies show that dendritic spines are dynamic structures. Their rapid creation, destruction and shape-changing are essential for short- and long-term plasticity at excitatory synapses on pyramidal neurons in the cerebral cortex. The onset of long-term potentiation, spine-volume growth and an increase in receptor trafficking are coincident, enabling a 'functional readout' of spine structure that links the age, size, strength and lifetime of a synapse. Spine dynamics are also implicated in long-term memory and cognition: intrinsic fluctuations in volume can explain synapse maintenance over long periods, and rapid, activity-triggered plasticity can relate directly to cognitive processes. Thus, spine dynamics are cellular phenomena with important implications for cognition and memory. Furthermore, impaired spine dynamics can cause psychiatric and neurodevelopmental disorders. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway.

            N Perkins (2006)
            The diverse cellular and biological functions of the nuclear factor kappa B (NF-kappaB) pathway, together with the catastrophic consequences of its aberrant regulation, demand specific and highly regulated control of its activity. As described in this review, regulation of the NF-kappaB pathway is brought about through multiple post-translational modifications that control the activity of the core components of NF-kappaB signaling: the IkappaB kinase (IKK) complex, the IkappaB proteins and the NF-kappaB subunits themselves. These regulatory modifications, which include phosphorylation, ubiquitination, acetylation, sumoylation and nitrosylation, can vary, depending on the nature of the NF-kappaB-inducing stimulus. Moreover, they frequently have distinct, sometimes antagonistic, functional consequences and the same modification can have different effects depending on the context. Given the important role of NF-kappaB in human health and disease, understanding these pathways will not only provide valuable insights into mechanism and function, but could also lead to new drug targets and the development of diagnostic and prognostic biomarkers for many pathological conditions.
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              Experience leaves a lasting structural trace in cortical circuits

              Sensory experiences exert a powerful influence on the function and future performance of neuronal circuits in the mammalian neocortex1-3. Restructuring of synaptic connections is believed to be one mechanism by which cortical circuits store information about the sensory world4,5. Excitatory synaptic structures, such as dendritic spines, are dynamic entities6-8 which remain sensitive to alteration of sensory input throughout life6,9. It remains unclear, however, whether structural changes at the level of dendritic spines can outlast the original experience and thereby provide a morphological basis for long-term information storage. Here we follow spine dynamics on apical dendrites of pyramidal neurons in functionally-defined regions of adult mouse visual cortex during plasticity of eye-specific responses induced by repeated closure of one eye (monocular deprivation, MD). The first MD episode doubled the rate of spine formation, thereby increasing spine density. This effect was specific to layer 5 cells located in binocular cortex where most neurons increase their responsiveness to the non-deprived eye3,10. Restoring binocular vision returned spine dynamics to baseline levels, but absolute spine density remained elevated and many MD-induced spines persisted during this period of functional recovery. Remarkably, spine addition did not increase again when the same eye was closed for the second time. This absence of structural plasticity stands out against the robust changes of eye specific responses which occur even faster upon repeated deprivation3. Thus, spines added during the first MD experience might provide a structural basis for subsequent functional shifts. These results provide a strong link between functional plasticity and specific synaptic rearrangements, revealing a mechanism of how prior experiences could be stored in cortical circuits.
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                Author and article information

                Contributors
                Journal
                Trends Neurosci
                Trends Neurosci
                Trends in Neurosciences
                Elsevier Applied Science Publishing
                0166-2236
                1878-108X
                June 2011
                June 2011
                : 34
                : 6-4
                : 316-325
                Affiliations
                Cardiff School of Biosciences, University of Cardiff, Biomedical Sciences Building 3, Cardiff CF10 3AT, UK
                Author notes
                [*]

                Current address: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Univesitaria, México D.F., México.

                Article
                TINS820
                10.1016/j.tins.2011.03.001
                3115056
                21459462
                8d6fde09-d155-4768-b7b2-d973a6b591e2
                © 2011 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

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                Neurosciences
                Neurosciences

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