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

Stromal interaction molecule (STIM) proteins play a crucial role in store-operated calcium entry (SOCE) as endoplasmic reticulum Ca²⁺ 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 Ca²⁺ activity was measured in vivo in neurons that expressed the GCaMP5G sensor. Optic tectum neurons in stim2a fish had more frequent Ca²⁺ 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 Ca²⁺ homeostasis and signaling.