Knockout of stim2a Increases Calcium Oscillations in Neurons and Induces Hyperactive-Like Phenotype in Zebrafish Larvae.

Stromal interaction molecule (STIM) proteins play a crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca ²⁺ sensors. In neurons, STIM2 was shown to have distinct functions from STIM1. However, its role in brain activity and behavior was not fully elucidated. The present study analyzed behavior in zebrafish ( Danio rerio ) that lacked stim2a . The mutant animals had no morphological abnormalities and were fertile. RNA-sequencing revealed alterations of the expression of transcription factor genes and several members of the calcium toolkit. Neuronal Ca ²⁺ activity was measured in vivo in neurons that expressed the GCaMP5G sensor. Optic tectum neurons in stim2a ^-/- fish had more frequent Ca ²⁺ signal oscillations compared with neurons in wildtype (WT) fish. We detected an increase in activity during the visual-motor response test, an increase in thigmotaxis in the open field test, and the disruption of phototaxis in the dark/light preference test in stim2a ^-/- mutants compared with WT. Both groups of animals reacted to glutamate and pentylenetetrazol with an increase in activity during the visual-motor response test, with no major differences between groups. Altogether, our results suggest that the hyperactive-like phenotype of stim2a ^-/- mutant zebrafish is caused by the dysregulation of Ca ²⁺ homeostasis and signaling.