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Secretagogin is a member of \u201cneuron\u2010specific\u201d Ca<jats:sup>2+<\/jats:sup>\u2010sensor proteins, yet variations in its expression due, chiefly, to neuronal activity remain ambiguous. We aimed to fill this gap of knowledge both in its use as a cell identity marker and for mechanistic analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We mapped secretagogin distribution in human foetal forebrains. Then, <jats:italic>Scgn<\/jats:italic>\u2010iCre::Ai9 mice in conjunction with single\u2010cell RNA\u2010seq were used to molecularly characterize cortical secretagogin\u2010expressing neurons. Besides the in\u00a0vitro manipulation of both SH\u2010SY5Y neuroblastoma cells and primary cortical cultures from foetal mice, the activity dependence of secretagogin expression was also studied upon systemic kainate administration and dark rearing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the mammalian brain, including humans, both transient and stable secretagogin expression sites exist. In the cerebral cortex, we identified deep\u2010layer pyramidal neurons with lifelong expression of secretagogin. Secretagogin expression was affected by neuronal activity: it was delayed in a cohort of human foetuses with Down's syndrome relative to age\u2010matched controls. In mice, dark rearing reduced secretagogin expression in the superior colliculus, a midbrain structure whose development is dependent on topographic visual inputs. In contrast, excitation by both KCl exposure of SH\u2010SY5Y cells and primary cortical neurons in\u00a0vitro and through systemic kainate administration in mice increased secretagogin expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We suggest that secretagogin expression in neurons is developmentally regulated and activity dependent.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70031","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T02:28:03Z","timestamp":1743560883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuronal activity modulates the expression of secretagogin, a Ca<sup>2+<\/sup> sensor protein, during mammalian forebrain development"],"prefix":"10.1111","volume":"241","author":[{"given":"J\u00e1nos","family":"Hanics","sequence":"first","affiliation":[{"name":"Department of Anatomy Semmelweis University  Budapest 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