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Nat Neurosci. 2014 Mar;17(3):400-6. doi: 10.1038/nn.3641. Epub 2014 Feb 2.

Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior.

Author information

1
1] Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy. [2].
2
1] Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia (IIT), Rovereto, Italy. [2] Institutions Markets Technology (IMT) Institute for Advanced Studies, Lucca, Italy.
3
Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Monterotondo, Italy.
4
Center for Life Nano Science, IIT, La Sapienza University, Rome, Italy.
5
Institute of Neuroinformatics, University of Z├╝rich and Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
6
Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia (IIT), Rovereto, Italy.
7
1] Department of Physiology and Pharmacology, La Sapienza University, Rome, Italy. [2] Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, Italy.

Abstract

Microglia are phagocytic cells that infiltrate the brain during development and have a role in the elimination of synapses during brain maturation. Changes in microglial morphology and gene expression have been associated with neurodevelopmental disorders. However, it remains unknown whether these changes are a primary cause or a secondary consequence of neuronal deficits. Here we tested whether a primary deficit in microglia was sufficient to induce some autism-related behavioral and functional connectivity deficits. Mice lacking the chemokine receptor Cx3cr1 exhibit a transient reduction of microglia during the early postnatal period and a consequent deficit in synaptic pruning. We show that deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes that have been previously associated with autism and other neurodevelopmental and neuropsychiatric disorders. These findings open the possibility that disruptions in microglia-mediated synaptic pruning could contribute to neurodevelopmental and neuropsychiatric disorders.

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PMID:
24487234
DOI:
10.1038/nn.3641
[Indexed for MEDLINE]
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