{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:20:07Z","timestamp":1779362407389,"version":"3.51.4"},"posted":{"date-parts":[[2025,2,8]]},"group-title":"Neuroscience","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Huntington\u2019s disease (HD) is a devastating movement disorder without a current cure. Although the monogenic basis of HD is well-defined, the complex downstream effects that underlie behavioral symptoms are poorly understood. These effects include cortical dysfunctions, yet the role of specific cortical neuronal subtypes in HD symptoms remain largely unexplored. Here, we used longitudinal\n                  <jats:italic>in vivo<\/jats:italic>\n                  two-photon calcium imaging to examine the activity of two cortical inhibitory neuron (IN) subtypes and excitatory corticostriatal projection neurons (CSPNs) in the motor cortex of R6\/2 HD mouse model throughout disease progression. We found that motor deficits in R6\/2 mice were accompanied by neuron type-specific abnormalities in movement-related activity, including hypoactivity of vasoactive intestinal peptide (VIP)-INs and CSPNs. Optogenetic activation of VIP-INs in R6\/2 mice restored healthy levels of activity in VIP-INs and their downstream CSPNs and ameliorated motor deficits in R6\/2 mice. Our findings highlight cortical INs as a potential therapeutic target for HD and possibly other neurological diseases.\n                <\/jats:p>","DOI":"10.1101\/2025.02.07.637155","type":"posted-content","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T23:50:21Z","timestamp":1739058621000},"source":"Crossref","is-referenced-by-count":2,"title":["Optogenetic restoration of neuron subtype-specific cortical activity ameliorates motor deficits in Huntington\u2019s Disease mice"],"prefix":"10.64898","author":[{"given":"Sonja","family":"Blumenstock","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Molecules \u2013 Signaling \u2013 Development, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"},{"name":"Molecular Neurodegeneration Group, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Arakelyan","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"del Grosso","sequence":"additional","affiliation":[{"name":"Department of Molecules \u2013 Signaling \u2013 Development, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Molecules \u2013 Signaling \u2013 Development, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enida","family":"Gjoni","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00fcdiger","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Molecules \u2013 Signaling \u2013 Development, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Dudanova","sequence":"additional","affiliation":[{"name":"Department of Molecules \u2013 Signaling \u2013 Development, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"},{"name":"Molecular Neurodegeneration Group, Max Planck Institute for Biological Intelligence, 82152 Martinsried, Germany"},{"name":"Center for Anatomy, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9609-4600","authenticated-orcid":false,"given":"Takaki","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Center for Neural Circuits and Behavior, and Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA"},{"name":"Hal\u0131c\u0131o\u011flu Data Science Institute, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041100250701000_2025.02.07.637155v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5994"},{"key":"2026041100250701000_2025.02.07.637155v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"2026041100250701000_2025.02.07.637155v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3469"},{"key":"2026041100250701000_2025.02.07.637155v1.4","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2016.00317"},{"key":"2026041100250701000_2025.02.07.637155v1.5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57017"},{"key":"2026041100250701000_2025.02.07.637155v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24162"},{"key":"2026041100250701000_2025.02.07.637155v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.09.030"},{"key":"2026041100250701000_2025.02.07.637155v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.03.025"},{"key":"2026041100250701000_2025.02.07.637155v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3446"},{"key":"2026041100250701000_2025.02.07.637155v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.04.031"},{"key":"2026041100250701000_2025.02.07.637155v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature12983"},{"key":"2026041100250701000_2025.02.07.637155v1.12","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01124.2015"},{"key":"2026041100250701000_2025.02.07.637155v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"2026041100250701000_2025.02.07.637155v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026041100250701000_2025.02.07.637155v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.07.026"},{"key":"2026041100250701000_2025.02.07.637155v1.16","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63377"},{"key":"2026041100250701000_2025.02.07.637155v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030159"},{"key":"2026041100250701000_2025.02.07.637155v1.18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55130"},{"key":"2026041100250701000_2025.02.07.637155v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4619"},{"key":"2026041100250701000_2025.02.07.637155v1.20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1592-09.2009"},{"key":"2026041100250701000_2025.02.07.637155v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43024-w"},{"key":"2026041100250701000_2025.02.07.637155v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.09.020"},{"key":"2026041100250701000_2025.02.07.637155v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.10.002"},{"key":"2026041100250701000_2025.02.07.637155v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.12.009"},{"key":"2026041100250701000_2025.02.07.637155v1.25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38744"},{"key":"2026041100250701000_2025.02.07.637155v1.26","first-page":"2372","article-title":"Cortical 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