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dc.contributor.authorGunner, Georgia
dc.contributor.authorJohnson, Kasey M.
dc.contributor.authorMondo, Erica
dc.contributor.authorLiu, Liwang
dc.contributor.authorTapper, Andrew R.
dc.contributor.authorSchafer, Dorothy P
dc.date2022-08-11T08:09:29.000
dc.date.accessioned2022-08-23T16:32:51Z
dc.date.available2022-08-23T16:32:51Z
dc.date.issued2019-07-01
dc.date.submitted2019-08-08
dc.identifier.citation<p>Nat Neurosci. 2019 Jul;22(7):1075-1088. doi: 10.1038/s41593-019-0419-y. Epub 2019 Jun 17. <a href="https://doi.org/10.1038/s41593-019-0419-y">Link to article on publisher's site</a></p>
dc.identifier.issn1097-6256 (Linking)
dc.identifier.doi10.1038/s41593-019-0419-y
dc.identifier.pmid31209379
dc.identifier.urihttp://hdl.handle.net/20.500.14038/37972
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractMicroglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. This synapse elimination is dependent on signaling by CX3CR1, the receptor for microglial fractalkine (also known as CXCL1), but not complement receptor 3. Furthermore, mice deficient in CX3CL1 have profound defects in synapse elimination. Single-cell RNA sequencing revealed that Cx3cl1 is derived from cortical neurons, and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and in microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1(-/-) and Cx3cl1(-/-) synapse elimination defects. Together, these results identify neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal that context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31209379&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1038/s41593-019-0419-y
dc.subjectCellular neuroscience
dc.subjectGlial biology
dc.subjectMolecular neuroscience
dc.subjectNeural circuits
dc.subjectNeuroscience
dc.subjectImmunopathology
dc.subjectMolecular and Cellular Neuroscience
dc.subjectNervous System
dc.titleSensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling
dc.typeJournal Article
dc.source.journaltitleNature neuroscience
dc.source.volume22
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/neurobiology_pp/245
dc.identifier.contextkey15082016
html.description.abstract<p>Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. This synapse elimination is dependent on signaling by CX3CR1, the receptor for microglial fractalkine (also known as CXCL1), but not complement receptor 3. Furthermore, mice deficient in CX3CL1 have profound defects in synapse elimination. Single-cell RNA sequencing revealed that Cx3cl1 is derived from cortical neurons, and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and in microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1(-/-) and Cx3cl1(-/-) synapse elimination defects. Together, these results identify neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal that context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.</p>
dc.identifier.submissionpathneurobiology_pp/245
dc.contributor.departmentGraduate School of Biomedical Sciences, Neuroscience Program
dc.contributor.departmentSchafer Lab
dc.contributor.departmentTapper Lab
dc.contributor.departmentBrudnick Neuropsychiatric Research Institute
dc.contributor.departmentNeurobiology
dc.source.pages1075-1088
dc.contributor.studentGeorgia Gunner
dc.contributor.studentErica Mondo
dc.description.thesisprogramNeuroscience


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