title: Microglia contact induces synapse formation in developing somatosensory cortex.
abstract: Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8-10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca(2+) transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.
authors: Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors: Akiko
authors: A
authors: Miyamoto
authors: Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.|Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama 240-0193, Japan.|Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 102-0076, Japan.
authors: Hiroaki
authors: H
authors: Wake
authors: Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama 240-0193, Japan.|Division of Visual Information Processing, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors: Ayako Wendy
authors: AW
authors: Ishikawa
authors: Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.|Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama 240-0193, Japan.
authors: Kei
authors: K
authors: Eto
authors: Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.|Department of Pharmacology, Graduated School of Medical and Engineering, Yamanashi University, Chuo 409-3898, Japan.
authors: Keisuke
authors: K
authors: Shibata
authors: Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 102-0076, Japan.|Section of Multiphoton Neuroimaging, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors: Hideji
authors: H
authors: Murakoshi
authors: Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.|Department of Pharmacology, Graduated School of Medical and Engineering, Yamanashi University, Chuo 409-3898, Japan.
authors: Schuichi
authors: 0000-0001-6184-3106
authors: S
authors: Koizumi
authors: School of Medical Sciences, The University of New South Wales, Sydney, New South Wales 2052, Australia.
authors: Andrew J
authors: AJ
authors: Moorhouse
authors: Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama 240-0193, Japan.|Division of Visual Information Processing, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors: Yumiko
authors: Y
authors: Yoshimura
authors: Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.|Department of Physiological Sciences, The Graduate School for Advanced Study, Hayama 240-0193, Japan.
authors: Junichi
authors: J
authors: Nabekura
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D007107:Immune System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology* / Q000648:ultrastructure; D036641:Microscopy, Fluorescence, Multiphoton; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D011554:Pseudopodia / Q000502:physiology / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D013003:Somatosensory Cortex / Q000196:embryology* / Q000648:ultrastructure; D013131:Spine / Q000196:embryology / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure