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Here, we use classical olfactory T-maze conditioning to assess behavior, combined with imaging to assess 5-HT and 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R levels within the underlying Mushroom Body (MB) brain circuitry. Null\n                    <jats:italic>dfmr1<\/jats:italic>\n                    mutants exhibit learning and memory deficits that are corrected by elevating 5-HT signaling via 1) overexpression of the serotonin biosynthetic enzyme tryptophan hydroxylase (Trhn) or 2) knockdown of the serotonin reuptake transporter (SERT). Direct comparisons reveal both Trhn and SERT manipulations equally restore learning and memory in\n                    <jats:italic>dfmr1<\/jats:italic>\n                    null mutants. 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R levels in the MB circuit are reduced relative to controls in\n                    <jats:italic>dfmr1<\/jats:italic>\n                    mutants, and 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R RNAi phenocopies\n                    <jats:italic>dfmr1<\/jats:italic>\n                    null behavioral deficits, suggesting these phenotypes are primarily caused by the loss of 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R signaling. Consistently, 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R overexpression in\n                    <jats:italic>dfmr1<\/jats:italic>\n                    nulls restores normal learning and memory compared to controls. These findings suggest loss of 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R signaling causes learning and memory deficits in this Fragile X syndrome model, and that rectifying this signaling impairment can restore learning and memory, providing a framework for serotonergic intervention strategies.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-34492-4","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T04:34:17Z","timestamp":1767760457000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated serotonin receptor 2A signaling restores learning and memory in a Fragile X syndrome model"],"prefix":"10.1038","volume":"16","author":[{"given":"Yuchen","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa K.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Mellies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendal","family":"Broadie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"34492_CR1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1176\/appi.neuropsych.21110282","volume":"35","author":"J Flavell","year":"2023","unstructured":"Flavell, J., Franklin, C. & Nestor, P. 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