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Impairment of the vestibulocerebellum (VC), including the flocculus (FL), has been shown to affect vertical gaze holding, indicating that the INC cooperates with the VC in controlling this function. However, a network between the INC and VC has not been identified. In this study, we aimed to obtain anatomical evidence of a neural pathway from the INC to the VC (the INC-VC pathway) in rats. Injection of dextran-conjugated Alexa Fluor 488 or adeno-associated virus 2-retro (AAV2retro) expressing GFP into the FL or another VC region (uvula\/nodulus) did not reveal any retrogradely labeled neurons in the INC, suggesting that INC neurons do not project directly to the VC. Rabies virus-based transsynaptic tracing experiments revealed that the INC-VC pathway is mediated via synaptic connections with the prepositus hypoglossi nucleus (PHN) and medial vestibular nucleus (MVN). The INC neurons in the INC-VC pathway were mainly localized bilaterally within the rostral region of the INC. Transsynaptic tracing experiments involving the INC-FL pathway revealed that INC neurons connected to the FL via the bilateral PHN and MVN. These results indicate that the INC-VC pathway is not a direct pathway but is mediated via the PHN and MVN. These findings can provide clues for understanding the network mechanisms responsible for vertical gaze holding.<\/jats:p>","DOI":"10.1523\/eneuro.0294-24.2024","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T17:50:16Z","timestamp":1730137816000},"page":"ENEURO.0294-24.2024","source":"Crossref","is-referenced-by-count":2,"title":["An Indirect Pathway from the Rat Interstitial Nucleus of Cajal to the Vestibulocerebellum Involved in Vertical Gaze Holding"],"prefix":"10.1523","volume":"11","author":[{"given":"Taketoshi","family":"Sugimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Miyashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-6597","authenticated-orcid":false,"given":"Yasuhiko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jns.2009.02.356","article-title":"Vertical and horizontal integrator failure in a ponto-medullary infarction: a possible role for paramedian tract neurons","volume":"280","author":"Anagnostou","year":"2009","journal-title":"J Neurol Sci"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.2","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1002\/cne.24853","article-title":"Heterogeneous vestibulocerebellar mossy fiber projections revealed by single axon reconstruction in the mouse","volume":"528","author":"Ando","year":"2020","journal-title":"J Comp Neurol"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90278-X"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.4","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(84)90160-5"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.1749-6632.1992.tb25236.x","article-title":"Cholinergic innervation of the cerebellum of the rat by secondary vestibular afferents","volume":"656","author":"Barmack","year":"1992","journal-title":"Ann N Y Acad Sci"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.6","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903170304"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1097\/WNO.0000000000000456","article-title":"Cerebellar control of eye movements","volume":"37","author":"Beh","year":"2017","journal-title":"J Neuroophthalmol"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.8","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902680103"},{"key":"2024110610501084000_11.11.ENEURO.0294-24.2024.9","doi-asserted-by":"crossref","unstructured":"Bertolini G , Romano F , Feddermann-Demont N , Straumann D , Tarnutzer AA , Ramat S (2019) Non-linearity in gaze holding: experimental results and possible mechanisms , Ed. 1. 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