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INTRODUCTION: Neurons code sensory information in Ca2+ spiking trains at discrete points in time and facilitate synaptic plasticity and synchronicity in the neurons. Ca2+ can enter the cytoplasm through gated ion channels. One of the regulatory mechanisms of Ca2+ homeostasis in neurons is Store-operated Ca2+ entry (nSOCE). When Ca2+ is depleted from the endoplasmic reticulum (ER: a major store of Ca2+), the decreased level of Ca2+ is sensed by STIM proteins (ER residents), which then oligomerize and interact with Ca2+ channels at the plasma membrane. This leads to Ca2+ influx and refilling ER with these ions by Ca2+‑ATPase. Analysis of parameters of the neuronal spontaneous Ca2+ oscillations in vivo and those in response to the external stimuli. Zebrafish larva is an exceptional model for whole‑brain functional imaging. However, the mechanisms underlying the spontaneous neuronal Ca2+ activity patterns, and their biological relevance, remain elusive. METHOD(S): Using Lightsheet Microscopy, we performed in vivo imaging of transgenic fish expressing GCaMP5G (a genetically encoded Ca2+ probe) under the neuronal promoter (Tg(elavl3: GCaMP5). The parameters of Ca2+ oscillations, such as the interspike intervals (ISI) and the Ca2+ amplitudes, were analyzed in neuronal somata of the three different regions of the brain (optic tectum (OT), cerebellum (Cereb), and inferior olive (IO)) of transgenic (TG), wild-type (WT), and stim2b‑/‑ zebrafish lines. RESULTS: Using MATLAB algorithms, we quantified the differences in Ca2+ oscillations patterns between regions in the brain neurons and showed that Ca2+ oscillations change significantly in stim2b‑/‑ fish. ISI was reduced, and Ca2+ amplitude was increased in stim2b‑/‑ as compared to transgenic WT in fish treated with a high concentration of Ca2+. CONCLUSIONS: This Ca2+ spiking trains modulation by Stim2b protein suggests its role in attenuation of Ca2+ buffering.