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Among these, is the GNAO1 disorder a severe pediatric encephalopathy associated with mutations in a gene encoding G protein subunit G\u03b1o, a key transducer of neuromodulatory responses mediated by a vast number of G protein\u2013coupled receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we introduce a unique approach to modeling GNAO1 disorder, and neurodevelopmental disorders in general, by creating a conditional knock\u2010in mouse model of a severe dominant negative GNAO1 variant G203R that allows circuit\u2010specific induction of the mutation. A comprehensive battery of behavioral tests, together with electrophysiological recordings and proteomic analysis, was used to assess motor performance, seizure susceptibility, as well as molecular and functional alterations associated with the disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The model allowed parsing out circuit\u2010specific contributions of G\u03b1o dysfunction to motor and epileptic manifestations across neurons in striatum and forebrain. We further established molecular profiles of the disorder in a region\u2010specific manner and documented the impact on synaptic transmission. This information guided the development of an intervention strategy using caffeine, which effectively rescued motor abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results point to the essential role of G\u03b1o in maintaining neural circuit homeostasis. This advances our understanding of GNAO1 disorder\u2010related disease mechanisms and lays foundation for rational, circuit\u2010based therapeutic strategies. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70276","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:30:31Z","timestamp":1774690231000},"page":"1528-1541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Conditional Modeling of\n                    <scp>GNAO1<\/scp>\n                    Disorder Dissociates Circuit Specific Contributions to Pathology and Rationalizes Ameliorative Strategies"],"prefix":"10.1002","volume":"41","author":[{"given":"Gloria","family":"Brunori","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Zucca","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology University of Florida  Jupiter Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colten K.","family":"Lankford","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine Northwestern 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