Spino-dendritic cross-talk in rodent Purkinje neurons mediated by endogenous Ca2+-binding proteins

The range of actions of the second messenger Ca2+ is a key determinant of neuronal excitability and plasticity. For dendritic spines, there is on-going debate regarding how diffusional efflux of Ca2+ affects spine signalling. However, the consequences of spino-dendritic coupling for dendritic Ca2+ homeostasis and downstream signalling cascades have not been explored to date. We addressed this question by four-dimensional computer simulations, which were based on Ca2+-imaging data from mice that either express or lack distinct endogenous Ca2+-binding proteins. Our simulations revealed that single active spines do not affect dendritic Ca2+ signalling. Neighbouring, coactive spines, however, induce sizeable increases in dendritic [Ca2+](i) when they process slow synaptic Ca2+ signals, such as those implicated in the induction of long-term plasticity. This spino-dendritic coupling is mediated by buffered diffusion, specifically by diffusing calbindin-bound Ca2+. This represents a central mechanism for activating calmodulin in dendritic shafts and therefore a novel form of signal integration in spiny dendrites.