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

Yang Zhan, Rosa C. Paolicelli, Francesco Sforazzini, Laetitia Weinhard, Giulia Bolasco, Francesca Pagani, Alexei L. Vyssotski, Angelo Bifone, Alessandro Gozzi, Davide Ragozzino, Cornelius T. Gross

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)400-406
Number of pages7
JournalNature Neuroscience
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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