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

The range of actions of the second messenger Ca 2+ is a key determinant of neuronal excitability and plasticity. For dendritic spines, there is on-going debate regarding how diffusional efflux of Ca 2+ affects spine signalling. However, the consequences of spino-dendritic coupling for dendritic Ca 2+ homeostasis and downstream signalling cascades have not been explored to date. We addressed this question by four-dimensional computer simulations, which were based on Ca 2+ -imaging data from mice that either express or lack distinct endogenous Ca 2+ -binding proteins. Our simulations revealed that single active spines do not affect dendritic Ca 2+ signalling. Neighbouring, coactive spines, however, induce sizeable increases in dendritic [Ca 2+ ] i when they process slow synaptic Ca 2+ 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 Ca 2+ . This represents a central mechanism for activating calmodulin in dendritic shafts and therefore a novel form of signal integration in spiny dendrites.