Neuronal activity modulates the expression of secretagogin, a Ca(2+) sensor protein, during mammalian forebrain development.

AIM: Because of their stable expression, some EF-hand Ca(2+)-binding proteins are broadly used as histochemical markers of neurons in the nervous system. Secretagogin is a member of "neuron-specific" Ca(2+)-sensor 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. METHODS: We mapped secretagogin distribution in human foetal forebrains. Then, Scgn-iCre::Ai9 mice in conjunction with single-cell RNA-seq were used to molecularly characterize cortical secretagogin-expressing neurons. Besides the in vitro manipulation of both SH-SY5Y 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. RESULTS: In the mammalian brain, including humans, both transient and stable secretagogin expression sites exist. In the cerebral cortex, we identified deep-layer 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-matched 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-SY5Y cells and primary cortical neurons in vitro and through systemic kainate administration in mice increased secretagogin expression. CONCLUSION: We suggest that secretagogin expression in neurons is developmentally regulated and activity dependent.