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      Astrocytes, neurons, synapses: a tripartite view on cortical circuit development

      review-article
      ,
      Neural Development
      BioMed Central
      Astrocyte, Neuron, Synapse, Development, Cortex

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          Abstract

          In the mammalian cerebral cortex neurons are arranged in specific layers and form connections both within the cortex and with other brain regions, thus forming a complex mesh of specialized synaptic connections comprising distinct circuits. The correct establishment of these connections during development is crucial for the proper function of the brain. Astrocytes, a major type of glial cell, are important regulators of synapse formation and function during development. While neurogenesis precedes astrogenesis in the cortex, neuronal synapses only begin to form after astrocytes have been generated, concurrent with neuronal branching and process elaboration. Here we provide a combined overview of the developmental processes of synapse and circuit formation in the rodent cortex, emphasizing the timeline of both neuronal and astrocytic development and maturation. We further discuss the role of astrocytes at the synapse, focusing on astrocyte-synapse contact and the role of synapse-related proteins in promoting formation of distinct cortical circuits.

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          Most cited references99

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          Interneurons of the neocortical inhibitory system.

          Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.
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            Neuronal circuits of the neocortex.

            We explore the extent to which neocortical circuits generalize, i.e., to what extent can neocortical neurons and the circuits they form be considered as canonical? We find that, as has long been suspected by cortical neuroanatomists, the same basic laminar and tangential organization of the excitatory neurons of the neocortex is evident wherever it has been sought. Similarly, the inhibitory neurons show characteristic morphology and patterns of connections throughout the neocortex. We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local patches of cortex, and within areas, cooperate to explore all possible interpretations of different cortical input and cooperatively select an interpretation consistent with their various cortical and subcortical inputs.
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              Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.

              An in situ study of mRNAs encoding NMDA receptor subunits in the developing rat CNS revealed that, at all stages, the NR1 gene is expressed in virtually all neurons, whereas the four NR2 transcripts display distinct expression patterns. NR2B and NR2D mRNAs occur prenatally, whereas NR2A and NR2C mRNAs are first detected near birth. All transcripts except NR2D peak around P20. NR2D mRNA, present mainly in midbrain structures, peaks around P7 and thereafter decreases to adult levels. Postnatally, NR2B and NR2C transcript levels change in opposite directions in the cerebellar internal granule cell layer. In the adult hippocampus, NR2A and NR2B mRNAs are prominent in CA1 and CA3 pyramidal cells, but NR2C and NR2D mRNAs occur in different subsets of interneurons. Recombinant binary NR1-NR2 channels show comparable Ca2+ permeabilities, but marked differences in voltage-dependent Mg2+ block and in offset decay time constants. Thus, the distinct expression profiles and functional properties of NR2 subunits provide a basis for NMDA channel heterogeneity in the brain.
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                Author and article information

                Contributors
                ifarhy@salk.edu
                nallen@salk.edu
                Journal
                Neural Dev
                Neural Dev
                Neural Development
                BioMed Central (London )
                1749-8104
                1 May 2018
                1 May 2018
                2018
                : 13
                : 7
                Affiliations
                ISNI 0000 0001 0662 7144, GRID grid.250671.7, Molecular Neurobiology Laboratory, , Salk Institute for Biological Studies, ; 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA
                Author information
                http://orcid.org/0000-0002-7542-5930
                Article
                104
                10.1186/s13064-018-0104-y
                5928581
                29712572
                d45e712e-c967-4ceb-abdf-e15b7c509679
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 January 2018
                : 17 April 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Neurosciences
                astrocyte,neuron,synapse,development,cortex
                Neurosciences
                astrocyte, neuron, synapse, development, cortex

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