ABSTRACT Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral

and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of

double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy. We found that

peripheral immune activation caused dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in multiple learning tasks in mice. These observed synaptic

highlight CX3CR1high monocytes and TNF-α as potential therapeutic targets for preventing infection-induced cognitive dysfunction. Access through your institution Buy or subscribe This is a

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PHAGOCYTE-MEDIATED SYNAPSE REMOVAL IN CORTICAL

NEUROINFLAMMATION IS PROMOTED BY LOCAL CALCIUM ACCUMULATION Article 25 January 2021 SARS-COV-2 PROMOTES MICROGLIAL SYNAPSE ELIMINATION IN HUMAN BRAIN ORGANOIDS Article Open access 05 October

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only under defined host conditions. _Nat. Neurosci._ 10, 1544–1553 (2007). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank W.B. Gan (New York University)

for the _Cx3cr1_–CreER mice and D.R. Littman (New York University) for the _Cx3cr1_–GFP mice. We also thank W.B. Gan and M.V. Bennett for critical reading of the manuscript. This work was

supported by a Whitehall Foundation Research Grant (G.Y.), the US National Institutes of Health grants R01GM107469 (G.Y.) and R21AG048410 (G.Y.) and a National Council for Scientific and

Technological Development (CNPq) (Brazil) fellowship (H.M.S.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Anesthesiology, Perioperative Care and Pain Medicine, New York

University (NYU) School of Medicine, New York, New York, USA Juan Mauricio Garré & Guang Yang * Departments of Pathology and Medicine, Skirball Institute of Biomolecular Medicine, New

York University School of Medicine, New York, New York, USA Hernandez Moura Silva & Juan J Lafaille Authors * Juan Mauricio Garré View author publications You can also search for this

author inPubMed Google Scholar * Hernandez Moura Silva View author publications You can also search for this author inPubMed Google Scholar * Juan J Lafaille View author publications You can

also search for this author inPubMed Google Scholar * Guang Yang View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS J.M.G., H.M.S., J.J.L.

and G.Y. designed the experiments; J.M.G. performed the _in vivo_ imaging experiments, animal behavior assays and biochemical experiments; J.M.G. and H.M.S. performed the flow cytometry

experiments; all authors contributed to the data analysis and interpretation; and J.M.G. and G.Y. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Guang Yang. ETHICS DECLARATIONS

COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–17, Supplementary Table 1 and

Supplementary Notes 1–2. (PDF 3709 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Garré, J., Silva, H., Lafaille, J. _et al._ CX3CR1+ monocytes

modulate learning and learning-dependent dendritic spine remodeling via TNF-α. _Nat Med_ 23, 714–722 (2017). https://doi.org/10.1038/nm.4340 Download citation * Received: 12 May 2016 *

Accepted: 11 April 2017 * Published: 15 May 2017 * Issue Date: June 2017 * DOI: https://doi.org/10.1038/nm.4340 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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