Manganese has emerged as an easily accessible and promising positive contrast agent for magnetic resonance imaging (MRI) that covers a broad spectrum of functional and anatomical applications in a wide variety of small-animal models. In modern science, each step, from the initial activation to the ultimate structural modification, can be analyzed using a variety of techniques. However, few techniques combine the potential of longterm in vivo observations with sensitivity to cellular activity and network functions that involve multiple brain structures. Certain features of neuronal function such as topographical organization of the cortex can only be investigated in intact animals. An alternative solution would be to design a contrast agent that enters the cell during the execution of a behavioral task and remains in stable concentrations when this task is finished. The use of manganese as an MRI contrast agent to highlight activities in excitable tissues largely depends on its properties to enter cells via voltage-gated or even ligand-gated Ca channels.