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Title: The microglial fractalkine receptor is not required for activity-dependent plasticity in the mouse visual system.

Authors: Lowery, Rebecca L; Tremblay, Marie-Eve; Hopkins, Brittany E; Majewska, Ania K

Published In Glia, (2017 Nov)

Abstract: Microglia have recently been implicated as key regulators of activity-dependent plasticity, where they contribute to the removal of inappropriate or excess synapses. However, the molecular mechanisms that mediate this microglial function are still not well understood. Although multiple studies have implicated fractalkine signaling as a mediator of microglia-neuron communications during synaptic plasticity, it is unclear whether this is a universal signaling mechanism or whether its role is limited to specific brain regions and stages of the lifespan. Here, we examined whether fractalkine signaling mediates microglial contributions to activity-dependent plasticity in the developing and adolescent visual system. Using genetic ablation of fractalkine's cognate receptor, CX3 CR1, and both ex vivo characterization and in vivo imaging in mice, we examined whether fractalkine signaling is required for microglial dynamics and modulation of synapses, as well as activity-dependent plasticity in the visual system. We did not find a role for fractalkine signaling in mediating microglial properties during visual plasticity. Ablation of CX3 CR1 had no effect on microglial density, distribution, morphology, or motility, in either adolescent or young adult mice across brain regions that include the visual cortex. Ablation of CX3 CR1 also had no effect on baseline synaptic turnover or contact dynamics between microglia and neurons. Finally, we found that fractalkine signaling is not required for either early or late forms of activity-dependent visual system plasticity. These findings suggest that fractalkine is not a universal regulator of synaptic plasticity, but rather has heterogeneous roles in specific brain regions and life stages.

PubMed ID: 28836393 Exiting the NIEHS site

MeSH Terms: Age Factors; Animals; Animals, Newborn; Antibodies/administration & dosage; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; CX3C Chemokine Receptor 1/genetics; CX3C Chemokine Receptor 1/immunology; CX3C Chemokine Receptor 1/metabolism*; Chemokine CX3CL1/metabolism; Dendritic Spines/ultrastructure; Gene Expression Regulation, Developmental/genetics*; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Luminescent Proteins/genetics; Luminescent Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia/drug effects; Microglia/physiology*; Neuronal Plasticity/drug effects; Neuronal Plasticity/genetics; Neuronal Plasticity/physiology*; Neurons/ultrastructure; Sensory Deprivation/physiology*; Signal Transduction/physiology; Visual Cortex/cytology; Visual Cortex/growth & development; Visual Cortex/metabolism; Visual Pathways/cytology*; Visual Pathways/drug effects; Visual Pathways/growth & development

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