An Inconvenient Truth: Calcium Sensors Are Calcium Buffers

Recent advances in Ca²⁺ imaging have given neuroscientists a tool to follow the activity of large numbers of individual neurons simultaneously in vivo in the brains of animals as they are presented with sensory stimulation, respond to environmental challenges, and engage in behaviors. The Ca²⁺ sensors used to transduce changes in cellular Ca²⁺ into changes in fluorescence must bind Ca²⁺ to produce a signal. By binding Ca²⁺, these sensors can act as buffers, often reducing the magnitude of a Ca²⁺ change severalfold, and producing a proportional slowing of the rates of change. Ca²⁺ probes can thus distort the patterns of activity they are intended to study and modify ongoing Ca²⁺ signaling functions. Recognizing these factors will enhance the use of in vivo Ca²⁺ imaging in the investigation of neural circuit function.