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Little is known of how ASD-risk genes regulate callosal connectivity. Here, we show that\n                    <jats:italic>Fmr1<\/jats:italic>\n                    , whose loss-of-function leads to Fragile X Syndrome (FXS), cell autonomously promotes maturation of callosal excitatory synapses between somatosensory barrel cortices in mice. Postnatal, cell-autonomous deletion of\n                    <jats:italic>Fmr1<\/jats:italic>\n                    in postsynaptic Layer (L) 2\/3 or L5 neurons results in a selective weakening of AMPA receptor- (R), but not NMDA receptor-, mediated callosal synaptic function, indicative of immature synapses. Sensory deprivation by contralateral whisker trimming normalizes callosal input strength, suggesting that experience-driven activity of postsynaptic\n                    <jats:italic>Fmr1<\/jats:italic>\n                    KO L2\/3 neurons weakens callosal synapses. In contrast to callosal inputs, synapses originating from local L4 and L2\/3 circuits are normal, revealing an input-specific role for postsynaptic\n                    <jats:italic>Fmr1<\/jats:italic>\n                    in regulation of synaptic connectivity within local and callosal neocortical circuits. These results suggest direct cell autonomous and postnatal roles for FMRP in development of specific cortical circuits and suggest a synaptic basis for long-range functional underconnectivity observed in FXS patients.\n                  <\/jats:p>","DOI":"10.7554\/elife.71555","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T08:00:27Z","timestamp":1633593627000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71555","source":"Crossref","is-referenced-by-count":22,"title":["Experience-dependent weakening of callosal synaptic connections in the absence of postsynaptic FMRP"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2859-3859","authenticated-orcid":true,"given":"Zhe","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neuroscience, O\u2019Donnell Brain Institute, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6279-0736","authenticated-orcid":true,"given":"Jay R","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, O\u2019Donnell Brain Institute, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-0661","authenticated-orcid":true,"given":"Kimberly M","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, O\u2019Donnell Brain Institute, University of Texas Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.neuron.2011.02.057","article-title":"Maturation of a 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