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Sensory experience is transduced into changes in gene transcription via the activation of calcium signaling pathways downstream of both L\u2010type voltage\u2010gated calcium channels (L\u2010<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>s) and<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>\u2010type glutamate receptors (<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s). These signaling pathways converge on the regulation of transcription factors including calcium\u2010response factor (Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>). Although Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>is dispensable for the transcriptional induction of<jats:italic>Bdnf<\/jats:italic>following the activation of L\u2010<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>s, here we show that the loss of Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>leads to enhanced<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010dependent transcription of<jats:italic>Bdnf<\/jats:italic>as well as<jats:italic>Arc<\/jats:italic>. We identify the<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>subunit\u2010encoding gene<jats:italic>Grin3a<\/jats:italic>as a regulatory target of Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>, and we show that expression of both<jats:italic>Carf<\/jats:italic>and<jats:italic>Grin3a<\/jats:italic>is depressed by the elevation of intracellular calcium, linking the function of this transcriptional regulatory pathway to neuronal activity. We find that light\u2010dependent activation of<jats:italic>Bdnf<\/jats:italic>and<jats:italic>Arc<\/jats:italic>transcription is enhanced in the visual cortex of young Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>knockout mice, suggesting a role for Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010dependent dampening of<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010dependent transcription in the developing brain. Finally, we demonstrate that enhanced<jats:italic>Bdnf<\/jats:italic>expression in Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>\u2010lacking neurons increases inhibitory synapse formation. Taken together, these data reveal a novel role for Ca<jats:styled-content style=\"fixed-case\">RF<\/jats:styled-content>as an upstream regulator of<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>\u2010dependent gene transcription and synapse formation in the developing brain.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13556-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>NMDARs promote brain development by inducing the transcription of genes, including brain\u2010derived neurotrophic factor (BDNF). We show that the transcription factor calcium\u2010response factor (CaRF) limits NMDAR\u2010dependent BDNF induction by regulating expression of the NMDAR subunit GluN3A. Loss of CaRF leads to enhanced BDNF\u2010dependent GABAergic synapse formation indicating the importance of this process for brain development. Our observation that both CaRF and GluN3A are down\u2010regulated by intracellular calcium suggests that this may be a mechanism for experience\u2010dependent modulation of synapse formation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13556","type":"journal-article","created":{"date-parts":[[2016,1,30]],"date-time":"2016-01-30T14:38:54Z","timestamp":1454164734000},"page":"164-176","source":"Crossref","is-referenced-by-count":21,"title":["The transcription factor calcium\u2010response factor limits<scp>NMDA<\/scp>receptor\u2010dependent transcription in the developing brain"],"prefix":"10.1111","volume":"137","author":[{"given":"Michelle R.","family":"Lyons","sequence":"first","affiliation":[{"name":"Department of Neurobiology Duke University Medical Center Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang\u2010Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Duke University Medical Center 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