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      Formation and Maintenance of Functional Spines in the Absence of Presynaptic Glutamate Release

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          Summary

          Dendritic spines are the major transmitter reception compartments of glutamatergic synapses in most principal neurons of the mammalian brain and play a key role in the function of nerve cell circuits. The formation of functional spine synapses is thought to be critically dependent on presynaptic glutamatergic signaling. By analyzing CA1 pyramidal neurons in mutant hippocampal slice cultures that are essentially devoid of presynaptic transmitter release, we demonstrate that the formation and maintenance of dendrites and functional spines are independent of synaptic glutamate release.

          Highlights

          • Elimination of presynaptic transmitter release in hippocampal organotypic slices

          • Dendrite growth and maintenance are independent of presynaptic glutamate release

          • Spine formation and maintenance are independent of presynaptic glutamate release

          • Recruitment of NMDA/AMPA receptors is independent of presynaptic glutamate release

          Abstract

          Spines are major neurotransmitter reception compartments of nerve cells. Contrary to the currently held dogma, Sigler et al. show that spine formation in the hippocampus is independent of synaptic neurotransmitter release, indicating that brain circuits are established by activity-independent cellular programs.

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          Most cited references43

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          Dendritic organization in the neurons of the visual and motor cortices of the cat.

          D SHOLL (1953)
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            The self-tuning neuron: synaptic scaling of excitatory synapses.

            Homeostatic synaptic scaling is a form of synaptic plasticity that adjusts the strength of all of a neuron's excitatory synapses up or down to stabilize firing. Current evidence suggests that neurons detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. Additional mechanisms may allow local or network-wide changes in activity to be sensed through parallel pathways, generating a nested set of homeostatic mechanisms that operate over different temporal and spatial scales.
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              A simple method for organotypic cultures of nervous tissue.

              Hippocampal slices prepared from 2-23-day-old neonates were maintained in culture at the interface between air and a culture medium. They were placed on a sterile, transparent and porous membrane and kept in petri dishes in an incubator. No plasma clot or roller drum were used. This method yields thin slices which remain 1-4 cell layers thick and are characterized by a well preserved organotypic organization. Pyramidal neurons labelled by extra- and intracellular application of horse radish peroxidase resemble by the organization and complexity of their dendritic processes those observed in situ at a comparable developmental stage. Excitatory and inhibitory synaptic potentials can easily be analysed using extra- or intracellular recording techniques. After a few days in culture, long-term potentiation of synaptic responses can reproducibly be induced. Evidence for a sprouting response during the first days in culture or following sections is illustrated. This technique may represent an interesting alternative to roller tube cultures for studies of the developmental changes occurring during the first days or weeks in culture.
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                Author and article information

                Contributors
                Journal
                Neuron
                Neuron
                Neuron
                Cell Press
                0896-6273
                1097-4199
                19 April 2017
                19 April 2017
                : 94
                : 2
                : 304-311.e4
                Affiliations
                [1 ]Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
                [2 ]Science Products GmbH, 65719 Hofheim am Taunus, Germany
                [3 ]Research Group Cellular Basis of Neural Circuit Plasticity, Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA
                [4 ]Max Planck Institute of Neurobiology, 82152 Martinsried, Germany
                Author notes
                []Corresponding author rhee@ 123456em.mpg.de
                [∗∗ ]Corresponding author brose@ 123456em.mpg.de
                [5]

                These authors contributed equally

                [6]

                Lead Contact

                Article
                S0896-6273(17)30241-6
                10.1016/j.neuron.2017.03.029
                5418202
                28426965
                bbbb7311-6512-4492-8517-4b7132bea235
                © 2017 The Authors. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 August 2016
                : 17 February 2017
                : 22 March 2017
                Categories
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                Neurosciences
                dendrite formation,spine formation,activity dependence,glutamate release,synaptogenesis,glutamate uncaging

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