Calcium is an important messenger in mammalian nerve cells. It mediates a variety of intracellular signal transduction pathways and plays an important role in regulating neuronal functions. Calcium signaling performs its highly specific functions in a defined subregion of the cell, especially in the cortex. Detection of calcium signals in neurons is particularly important to study neuronal functions. In this article, we review the method of detecting calcium signals in model animals. The common method include two-photon calcium imaging technology, deep brain microscopic calcium imaging technology, and optical fiber recording technology. Through a literature review and analysis, new developments in this field are presented. We also discuss the prospects of calcium signal detection to study cortical neuronal signals and plasticity in various animal models.