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The hypothalamus receives light\u2010related information via the retinohypothalamic tract (RHT). Here, we demonstrate that, in the mouse, a lateral branch of the RHT (l\u2010RHT) projects monosynaptically to orexin\u2010A (OX\u2010A) neurons in the perifornical hypothalamic area (PFH). Intravitreal injection of the anterograde tracer cholera toxin\u2010\u03b2 (CT\u03b2) filled most of the vesicular glutamate transporter (VGluT1)\/cannabinoid receptor 1 (CB1R)\u2010positive retinal\u2010derived inputs projecting to the OX\u2010A neurons. Monocular injection of Fluo4\u2010Dextran, a fluorimetric sensor of calcium mobilization, yielded fast labeling of these inputs 10\u2009min after eye exposure to blue light, concomitantly with the enhancement of hypothalamic 2\u2010arachidonoylglycerol (2\u2010AG) levels, and inhibition of OX\u2010A neuronal firing, an effect prevented by in\u00a0vivo administration of the CB1R antagonist AM251. Our findings provide anatomical and functional evidence of a selective retino\u2010hypothalamic network responsive to blue light, whose control should be suitable for therapies to counteract sleep disorders, seasonal affective disorder, or even conditions like narcolepsy or anxiety.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70137-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.70137","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T03:21:22Z","timestamp":1750476082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Blue Light\u2010Responsive Lateral Pathway of the Retinohypothalamic Tract Promotes 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