{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:29:33Z","timestamp":1768505373270,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,31]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Mutations in\n                  <jats:italic>MECP2<\/jats:italic>\n                  cause the neurodevelopmental disorder Rett syndrome.\n                  <jats:italic>MECP2<\/jats:italic>\n                  codes for methyl CpG binding protein 2 (MECP2), a transcriptional regulator that activates genetic programs for experience-dependent plasticity. Many neural and behavioral symptoms of Rett syndrome may result from dysregulated timing and threshold for plasticity. As a model of adult plasticity, we examine changes to auditory cortex inhibitory circuits in female mice when they are first exposed to pups; this plasticity facilitates behavioral responses to pups emitting distress calls. Brain-wide deletion of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  alters expression of markers associated with GABAergic parvalbumin interneurons (PVin) and impairs the emergence of pup retrieval. We hypothesized that loss of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  in PVin disproportionately contributes to the phenotype. Here we find that deletion of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  from PVin delayed the onset of maternal retrieval behavior and recapitulated the major molecular and neurophysiological features of brain-wide deletion of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  . We observed that when PVin-selective mutants were exposed to pups, auditory cortical expression of PVin markers increased relative to that in wild type littermates. PVin-specific mutants also failed to show the inhibitory auditory cortex plasticity seen in wild type mice upon exposure to pups and their vocalizations. Finally, using an intersectional viral genetic strategy, we demonstrate that post-developmental loss of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  in PVin of the auditory cortex is sufficient to delay onset of maternal retrieval. Our results support a model in which PVin play a central role in adult cortical plasticity and may be particularly impaired by loss of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  .\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>SIGNIFICANCE STATEMENT<\/jats:title>\n                  <jats:p>\n                    Rett syndrome is a neurodevelopmental disorder that includes deficits in both communication and the ability to update brain connections and activity during learning (\u2018plasticity\u2019). This condition is caused by mutations in the gene\n                    <jats:italic>MECP2<\/jats:italic>\n                    . We use a maternal behavioral test in mice requiring both vocal perception and neural plasticity to probe\n                    <jats:italic>Mecp2\u2019<\/jats:italic>\n                    s role in social and sensory learning.\n                    <jats:italic>Mecp2<\/jats:italic>\n                    is normally active in all brain cells, but here we remove it from a specific population (\u2018parvalbumin neurons\u2019). We find that this is sufficient to delay learned behavioral responses to pups and recreates many deficits seen in whole brain\n                    <jats:italic>Mecp2<\/jats:italic>\n                    deletion. Our findings suggest that parvalbumin neurons specifically are central to the consequences of loss of\n                    <jats:italic>Mecp2<\/jats:italic>\n                    activity and yield clues as to possible mechanisms by which Rett syndrome impairs brain function.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.01.30.526321","type":"posted-content","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T11:04:36Z","timestamp":1675163076000},"source":"Crossref","is-referenced-by-count":1,"title":["Selective deletion of\n                  <i>Methyl CpG binding protein 2<\/i>\n                  from parvalbumin interneurons in the auditory cortex delays the onset of maternal retrieval in mice"],"prefix":"10.64898","author":[{"given":"Deborah D.","family":"Rupert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexa","family":"Pagliaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Choe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6927-0189","authenticated-orcid":false,"given":"Stephen D.","family":"Shea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023020202400714000_2023.01.30.526321v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"2023020202400714000_2023.01.30.526321v1.2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015886123480"},{"key":"2023020202400714000_2023.01.30.526321v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh142"},{"key":"2023020202400714000_2023.01.30.526321v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(96)00544-8"},{"key":"2023020202400714000_2023.01.30.526321v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03814-7"},{"key":"2023020202400714000_2023.01.30.526321v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.07.015"},{"key":"2023020202400714000_2023.01.30.526321v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature08002"},{"key":"2023020202400714000_2023.01.30.526321v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq145"},{"key":"2023020202400714000_2023.01.30.526321v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3669"},{"key":"2023020202400714000_2023.01.30.526321v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.018"},{"key":"2023020202400714000_2023.01.30.526321v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature09582"},{"key":"2023020202400714000_2023.01.30.526321v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/85906"},{"key":"2023020202400714000_2023.01.30.526321v1.13","doi-asserted-by":"crossref","unstructured":"Cisneros-Franco JM , de Villers-Sidani E (2019) Reactivation of critical period plasticity in adult auditory cortex through chemogenetic silencing of parvalbumin-positive interneurons. 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