{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:55:47Z","timestamp":1768510547667,"version":"3.49.0"},"posted":{"date-parts":[[2024,4,5]]},"group-title":"Neuroscience","reference-count":27,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The heterotrimeric G-protein \u03b1 subunit, G\u03b1\n                  <jats:sub>olf<\/jats:sub>\n                  , acts to transduce extracellular signals through G-protein coupled receptors (GPCRs) and stimulates adenylyl cyclase mediated production of the second messenger cyclic adenosine monophosphate. Numerous mutations in the\n                  <jats:italic>GNAL<\/jats:italic>\n                  gene, which encodes G\u03b1\n                  <jats:sub>olf<\/jats:sub>\n                  , have been identified as causative for an adult-onset dystonia. These mutations disrupt GPCR signaling cascades in\n                  <jats:italic>in vitro<\/jats:italic>\n                  assays through several mechanisms, and this disrupted signaling is hypothesized to lead to dystonic motor symptoms in patients. However, the cells and circuits that mutations in\n                  <jats:italic>GNAL<\/jats:italic>\n                  corrupt are not well understood. Published patterns of G\u03b1\n                  <jats:sub>olf<\/jats:sub>\n                  expression outside the context of the striatum are sparse, conflicting, often lack cell type specificity, and may be confounded by expression of the close\n                  <jats:italic>GNAL<\/jats:italic>\n                  homolog of\n                  <jats:italic>GNAS<\/jats:italic>\n                  . Here, we use RNAScope in-situ hybridization to quantitatively characterize\n                  <jats:italic>Gnal<\/jats:italic>\n                  mRNA expression in brain tissue from wildtype C57BL\/6J adult mice. We observed widespread expression of\n                  <jats:italic>Gnal<\/jats:italic>\n                  puncta throughout the brain, suggesting G\u03b1\n                  <jats:sub>olf<\/jats:sub>\n                  is expressed in more brain structures and neuron types than previously accounted for. We quantify transcripts at a single cell level, and use neuron type specific markers to further classify and understand patterns of\n                  <jats:italic>GNAL<\/jats:italic>\n                  expression. Our data suggests that brain regions classically associated with motor control, initiation, and regulation show the highest expression of\n                  <jats:italic>GNAL<\/jats:italic>\n                  , with Purkinje Cells of the cerebellum showing the highest expression of any neuron type examined. Subsequent conditional\n                  <jats:italic>Gnal<\/jats:italic>\n                  knockout in Purkinje cells led to markedly decreased intracellular cAMP levels and downstream cAMP-dependent enzyme activation. Our work provides a detailed characterization of\n                  <jats:italic>Gnal<\/jats:italic>\n                  expression throughout the brain and the biochemical consequences of loss of G\u03b1\n                  <jats:sub>olf<\/jats:sub>\n                  signaling\n                  <jats:italic>in vivo<\/jats:italic>\n                  in neurons that highly express\n                  <jats:italic>Gnal<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.04.03.587766","type":"posted-content","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T22:05:11Z","timestamp":1712354711000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>G<\/i>\n                  \u03b1\n                  <i>\n                    <sub>olf<\/sub>\n                  <\/i>\n                  Regulates Biochemical Signaling in Neurons Associated with Movement Control and Initiation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-190X","authenticated-orcid":false,"given":"Michael","family":"Millett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anika","family":"Heuberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth Martin","family":"Castosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Comite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Gallardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2727-3327","authenticated-orcid":false,"given":"Nicole E","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lloyd","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8023-1313","authenticated-orcid":false,"given":"Mark S","family":"Moehle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024040907150932000_2024.04.03.587766v1.1","doi-asserted-by":"crossref","first-page":"e79135","DOI":"10.7554\/eLife.79135","article-title":"Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia","volume":"11","year":"2022","journal-title":"Elife"},{"issue":"2","key":"2024040907150932000_2024.04.03.587766v1.2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.3390\/cells9020506","article-title":"G-protein-coupled receptors in CNS: a potential therapeutic 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