Neuronal activity modulates the expression of secretagogin, a Ca2+ sensor protein, during mammalian forebrain development

Abstract

Aim

Because of their stable expression, some EF-hand Ca²⁺-binding proteins are broadly used as histochemical markers of neurons in the nervous system. Secretagogin is a member of “neuron-specific” Ca²⁺-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.