Abstract
Neurons require trophic support during neural circuit formation; however, how the cellular milieu contributes to neuronal survival remains unclear. We found that layer V cortical neurons require support from microglia for survival during postnatal development. Specifically, we found that microglia accumulated close to the subcerebral and callosal projection axons in the postnatal brain. Inactivation of microglia by minocycline treatment or transient ablation of microglia in CD11b-DTR transgenic mice led to increased apoptosis, specifically in layer V subcerebral and callosal projection neurons. CX3CR1 in microglia was required for the survival of layer V neurons. Microglia consistently promoted the survival of cortical neurons in vitro. In addition, we identified microglia-derived IGF1 as a trophic factor that maintained neuronal survival. Our results highlight a neuron-glia interaction that is indispensable for network formation during a specific period in the developing brain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology*
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CD11b Antigen / metabolism
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CX3C Chemokine Receptor 1
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Calcium-Binding Proteins / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cell Survival / drug effects
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Cell Survival / genetics
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Cells, Cultured
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Coculture Techniques
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Diphtheria Toxin / pharmacology
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / physiology*
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Humans
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microfilament Proteins / metabolism
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Microglia / drug effects
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Microglia / physiology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects
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Neurons / physiology*
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Receptors, Chemokine / deficiency
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Visual Cortex* / cytology
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Visual Cortex* / embryology
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Visual Cortex* / growth & development
Substances
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Aif1 protein, mouse
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CD11b Antigen
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CX3C Chemokine Receptor 1
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Calcium-Binding Proteins
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Cx3cr1 protein, mouse
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Diphtheria Toxin
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Enzyme Inhibitors
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Microfilament Proteins
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Nerve Tissue Proteins
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Receptors, Chemokine
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insulin-like growth factor-1, mouse
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Insulin-Like Growth Factor I
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Camk2a protein, mouse