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Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory "Barrel" cortex.

Abstract

Accumulative evidence indicates that microglial cells influence the normal development of central nervous system (CNS) synapses. Yet, the functional properties of microglia in relation with synapse development remain unclear. We recently showed that in layer 4 of the whisker-related barrel field of the mouse somatosensory cortex, microglial cells are recruited only after postnatal day (P)5 in the center of the barrels where thalamo-cortical synapses are concentrated and begin their maturation. In the present study, we analyzed the phenotype of microglia during this developmental process. We show that between P5 and P7 microglial cells acquire a more ramified morphology with a smaller soma, they express classical markers of microglia (Iba1, CD11b, and CD68) but never markers of activation (Mac-2 and MHCII) and rarely the proliferation marker Ki67. Electrophysiological recordings in acute cortical slices showed that at P5 a proportion of layer 4 microglia transiently express voltage-dependant potassium currents of the delayed rectifier family, mostly mediated by Kv1.3 subunits, which are usually expressed by activated microglia under pathological conditions. This proportion of cells with rectifying properties doubles between P5 and P6, in concomitance with the beginning of microglia invasion of the barrel centers. Finally, analysis of the responses mediated by purinergic receptors indicated that a higher percentage of rectifying microglia expressed functional P2Y6 and P2Y12 receptors, as compared with nonrectifying cells, whereas all cells expressed functional P2X7 receptors. Our results indicate that during normal cortical development distinct microglia properties mature differentially, some of them being exquisitely influenced by the local environment of the maturating neuronal network.

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  • Authors+Show Affiliations

    ,

    Inserm, U603, Paris, France; CNRS UMR, 8154, Paris, France; Paris Descartes University, Paris, France.

    , , , ,

    Source

    Glia 61:10 2013 Oct pg 1582-94

    MeSH

    Adaptation, Physiological
    Animals
    Animals, Newborn
    Antigens, CD
    Antigens, Differentiation
    Antigens, Differentiation, Myelomonocytic
    CD11b Antigen
    CX3C Chemokine Receptor 1
    Calcium-Binding Proteins
    Electric Stimulation
    Galectin 3
    Gene Expression Regulation, Developmental
    Green Fluorescent Proteins
    In Vitro Techniques
    Ki-67 Antigen
    Membrane Potentials
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Microfilament Proteins
    Microglia
    Nerve Tissue Proteins
    Phenotype
    Potassium Channel Blockers
    Receptors, Chemokine
    Receptors, Purinergic P2
    Receptors, Purinergic P2Y12
    Somatosensory Cortex
    Tetraethylammonium
    Uridine Diphosphate

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23893820

    Citation

    Arnoux, Isabelle, et al. "Adaptive Phenotype of Microglial Cells During the Normal Postnatal Development of the Somatosensory "Barrel" Cortex." Glia, vol. 61, no. 10, 2013, pp. 1582-94.
    Arnoux I, Hoshiko M, Mandavy L, et al. Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory "Barrel" cortex. Glia. 2013;61(10):1582-94.
    Arnoux, I., Hoshiko, M., Mandavy, L., Avignone, E., Yamamoto, N., & Audinat, E. (2013). Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory "Barrel" cortex. Glia, 61(10), pp. 1582-94. doi:10.1002/glia.22503.
    Arnoux I, et al. Adaptive Phenotype of Microglial Cells During the Normal Postnatal Development of the Somatosensory "Barrel" Cortex. Glia. 2013;61(10):1582-94. PubMed PMID: 23893820.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory "Barrel" cortex. AU - Arnoux,Isabelle, AU - Hoshiko,Maki, AU - Mandavy,Léo, AU - Avignone,Elena, AU - Yamamoto,Nobuhiko, AU - Audinat,Etienne, Y1 - 2013/07/26/ PY - 2012/11/14/received PY - 2013/03/08/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/3/29/medline KW - CD11b KW - CD68 KW - CX3CR1 KW - Kv1.3 KW - purinergic KW - signaling SP - 1582 EP - 94 JF - Glia JO - Glia VL - 61 IS - 10 N2 - Accumulative evidence indicates that microglial cells influence the normal development of central nervous system (CNS) synapses. Yet, the functional properties of microglia in relation with synapse development remain unclear. We recently showed that in layer 4 of the whisker-related barrel field of the mouse somatosensory cortex, microglial cells are recruited only after postnatal day (P)5 in the center of the barrels where thalamo-cortical synapses are concentrated and begin their maturation. In the present study, we analyzed the phenotype of microglia during this developmental process. We show that between P5 and P7 microglial cells acquire a more ramified morphology with a smaller soma, they express classical markers of microglia (Iba1, CD11b, and CD68) but never markers of activation (Mac-2 and MHCII) and rarely the proliferation marker Ki67. Electrophysiological recordings in acute cortical slices showed that at P5 a proportion of layer 4 microglia transiently express voltage-dependant potassium currents of the delayed rectifier family, mostly mediated by Kv1.3 subunits, which are usually expressed by activated microglia under pathological conditions. This proportion of cells with rectifying properties doubles between P5 and P6, in concomitance with the beginning of microglia invasion of the barrel centers. Finally, analysis of the responses mediated by purinergic receptors indicated that a higher percentage of rectifying microglia expressed functional P2Y6 and P2Y12 receptors, as compared with nonrectifying cells, whereas all cells expressed functional P2X7 receptors. Our results indicate that during normal cortical development distinct microglia properties mature differentially, some of them being exquisitely influenced by the local environment of the maturating neuronal network. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/23893820/Adaptive_phenotype_of_microglial_cells_during_the_normal_postnatal_development_of_the_somatosensory_ L2 - https://doi.org/10.1002/glia.22503 DB - PRIME DP - Unbound Medicine ER -