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      Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

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          Abstract

          Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine. Technical advances in monitoring molecular behaviors in single dendritic spines have revealed that each signaling pathway is differently regulated across multiple spatiotemporal domains. The spatial pattern of signaling activity expands from a single spine to the nearby dendritic area, dendritic branch and the nucleus, regulating different cellular events at each spatial scale. Temporally, biochemical events are typically triggered by short Ca 2+ pulses (~10–100 ms). However, these signals can then trigger activation of downstream protein cascades that can last from milliseconds to hours. Recent imaging studies provide many insights into the biochemical processes governing signaling events of molecular assemblies at different spatial localizations. Here, we highlight recent findings of signaling dynamics during synaptic plasticity and discuss their roles in long-term structural plasticity of dendritic spines.

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          A brain-specific microRNA regulates dendritic spine development.

          MicroRNAs are small, non-coding RNAs that control the translation of target messenger RNAs, thereby regulating critical aspects of plant and animal development. In the mammalian nervous system, the spatiotemporal control of mRNA translation has an important role in synaptic development and plasticity. Although a number of microRNAs have been isolated from the mammalian brain, neither the specific microRNAs that regulate synapse function nor their target mRNAs have been identified. Here we show that a brain-specific microRNA, miR-134, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines--postsynaptic sites of excitatory synaptic transmission. This effect is mediated by miR-134 inhibition of the translation of an mRNA encoding a protein kinase, Limk1, that controls spine development. Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and in this way may contribute to synaptic development, maturation and/or plasticity.
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            The molecular basis of CaMKII function in synaptic and behavioural memory.

            Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the primary model by which to study the cellular and molecular basis of memory. Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP induction, is persistently activated by stimuli that elicit LTP, and can, by itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII autophosphorylation and dephosphorylation indicates that this kinase could serve as a molecular switch that is capable of long-term memory storage. Consistent with such a role, mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory. These results make CaMKII a leading candidate in the search for the molecular basis of memory.
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              Extracellular vesicles round off communication in the nervous system.

              Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system.
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                Author and article information

                Contributors
                Journal
                Front Synaptic Neurosci
                Front Synaptic Neurosci
                Front. Synaptic Neurosci.
                Frontiers in Synaptic Neuroscience
                Frontiers Media S.A.
                1663-3563
                29 August 2018
                2018
                : 10
                : 29
                Affiliations
                Neuronal Signal Transduction, Max Planck Florida Institute for Neuroscience (MPFI) , Jupiter, FL, United States
                Author notes

                Edited by: George Augustine, Nanyang Technological University, Singapore

                Reviewed by: Toh Hean Ch’ng, Nanyang Technological University, Singapore; Marc Fivaz, University of Greenwich, United Kingdom

                *Correspondence: Ryohei Yasuda ryohei.yasuda@ 123456mpfi.org
                Article
                10.3389/fnsyn.2018.00029
                6123351
                30210329
                ee45f209-4526-4bb4-82c8-5f3ec9c36c13
                Copyright © 2018 Nakahata and Yasuda.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2018
                : 07 August 2018
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 166, Pages: 13, Words: 10955
                Funding
                Funded by: National Institute of Mental Health 10.13039/100000065
                Award ID: R01MH080047, R01MH111486
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Award ID: DP1NS096787
                Categories
                Neuroscience
                Review

                Neurosciences
                dendritic spine,calcium signaling,synaptic plasticity,actin cytoskeleton,camkii,small gtpase,fret flim,ltp

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