Genetic approaches are useful in biology because they provide an opportunity to understand any phenomenon at the level of molecules. When it is applied to the studies of animal behaviors, the goal is to understand the mechanism underlying various brain functions at levels spanning from molecules to behaviors. We have been studying the role of intracellular Ca2+ using genetics in the mouse. Intracellular Ca2+ is a critical element in the regulation of neuronal functions. The effectiveness of Ca2+ as a regulator of intracellular events is in part due to the fact that the concentration of Ca2+ in resting neurons is very low, ~0.1nM, and therefore a slight increase in the intracellular Ca2+ concentration can induce significant effects. There are two major sources of the intracellular Ca2+: the extracellular space and the internal Ca2+ stores. When a neuron is activated, extracellular Ca2+ enters the cytoplasm through diverse channels, including voltage-gated and ligand-gated Ca2+ channels. The increased cytoplasmic Ca2+ gets cleared efficiently to bring the cellular state back to a basal level through active processes, including the Na+/Ca2+ exchanger system. We have been studying the physiological functions of diverse molecules involved in the control of the intracellular Ca2+ level in neurons, through producing and analyzing mutant mice defective in those molecules. The tools of analysis include molecular biology, genetics, histology, physiology in vitro as well as in vivo, and behavior. The genes that we have studied and published so far include several subunits of voltage-gated Ca2+ channels (a1A, a1B, a1D, a1E, a1G, b3), the two Na+/Ca2+ exchangers (NCX-1 and NCX-2), and two phospholipaseCb isozymes (PLCb1 and b4). Several that are under current analyses include a1H, a1C and NCX-3. In my talk, I will briefly describe the salient features of these mutant mice, and then highlight some of the mutants in some detail.