{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:44:43Z","timestamp":1792039483739,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The neurodevelopmental disorder fragile X syndrome (FXS) results from hypermethylation of the\n                    <jats:italic>FMR1<\/jats:italic>\n                    gene, which prevents production of the FMRP protein. FMRP modulates the expression and function of a variety of proteins, including voltage\u2010gated ion channels, such as hyperpolarization\u2010activated and cyclic nucleotide\u2010gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders such as FXS. MD connectivity with the medial prefrontal cortex (mPFC) is integral to executive functions such as working memory and social behaviours that are disrupted in FXS. We used a combination of retrograde labelling and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    brain slice whole\u2010cell electrophysiology in 40 wild\u2010type and 42\n                    <jats:italic>Fmr1<\/jats:italic>\n                    knockout male mice to investigate how a lack of\n                    <jats:italic>Fmr1<\/jats:italic>\n                    affects intrinsic cellular properties in lateral (MD\u2010L) and medial (MD\u2010M) MD neurons that project to the mPFC (MD\u2192mPFC neurons). In MD\u2010L neurons,\n                    <jats:italic>Fmr1<\/jats:italic>\n                    knockout decreased the HCN\u2010mediated membrane properties voltage sag and membrane after\u2010hyperpolarization. We also identified a delay in rebound spike timing in both complex bursts and low\u2010threshold spikes. In\n                    <jats:italic>Fmr1<\/jats:italic>\n                    knockout mice, reduced HCN channel activity in MD\u2010L\u2192mPFC neurons impaired both the timing and the magnitude of HCN\u2010mediated membrane potential regulation. Changes in response timing might adversely affect rhythm propagation in\n                    <jats:italic>Fmr1<\/jats:italic>\n                    KO thalamocortical circuitry. MD thalamic neurons are crucial for maintaining rhythmic activity involved in cognitive and affective functions. Understanding specific mechanisms of thalamocortical circuit activity might lead to therapeutic interventions for individuals with FXS and other conditions characterized by thalamic dysrhythmia.\n                  <\/jats:p>","DOI":"10.1113\/ep092894","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T04:43:13Z","timestamp":1757047393000},"page":"1340-1364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Fmr1<\/i>\n                    \u00a0knockout disrupts multiple intrinsic properties via reduced HCN channel activity in mediodorsal thalamocortical neurons"],"prefix":"10.1113","volume":"111","author":[{"given":"Gregory J.","family":"Ordemann","sequence":"first","affiliation":[{"name":"Department of Neurology Dell Medical School at The University of Texas at Austin  Austin Texas USA"},{"name":"Center for Learning and Memory at The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Lyuboslavsky","sequence":"additional","affiliation":[{"name":"Department of Neurology Dell Medical School at The University of Texas at Austin  Austin Texas USA"},{"name":"Center for Learning and Memory at The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Kizimenko","sequence":"additional","affiliation":[{"name":"Department of Neurology Dell Medical School at The University of Texas at Austin  Austin Texas USA"},{"name":"Center for Learning and Memory at The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey C.","family":"Brumback","sequence":"additional","affiliation":[{"name":"Department of Neurology Dell Medical School at The University of Texas at Austin  Austin Texas USA"},{"name":"Center for Learning and Memory at The University of Texas at Austin  Austin Texas USA"},{"name":"Department of Pediatrics Dell Medical School at The University of Texas at Austin  Austin Texas 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