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Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the Ca<jats:sub>V<\/jats:sub>1.4 gain-of function mutation I756T (Ca<jats:sub>V<\/jats:sub>1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. Ca<jats:sub>V<\/jats:sub>1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca<jats:sup>2+<\/jats:sup> influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the Ca<jats:sub>V<\/jats:sub>1.4-IT mutation. Long term treatments with low-dose Ca<jats:sup>2+<\/jats:sup> channel blockers might however be beneficial reducing Ca<jats:sup>2+<\/jats:sup> toxicity without major effects on ganglion cells responses.<\/jats:p>","DOI":"10.1038\/s41598-021-82210-7","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T11:06:44Z","timestamp":1612177604000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Function of cone and cone-related pathways in CaV1.4 IT mice"],"prefix":"10.1038","volume":"11","author":[{"given":"Lucia","family":"Zanetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irem","family":"Kilicarslan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Netzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Babai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-4193","authenticated-orcid":false,"given":"Hartwig","family":"Seitter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-1166","authenticated-orcid":false,"given":"Alexandra","family":"Koschak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"82210_CR1","first-page":"2414","volume":"42","author":"CW Morgans","year":"2001","unstructured":"Morgans, C. 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