This paper reports the development of a new suite of genetically encoded calcium indicators (GECIs), designated NEMO, which exhibit fast kinetics and wide dynamic ranges (>100-fold). NEMOs demonstrate significantly larger peak signal-to-baseline ratios (SBRs) compared to existing GCaMP6 series, enabling the detection of subtle calcium transients and single action potentials in neurons. The high sensitivity and resolution of NEMO sensors make them suitable for monitoring neuronal activity and other calcium-modulated physiological processes in various organisms.