Dendritic spikes and their influence on extracellular calcium signaling

Extracellular calcium is critical for many neural functions, including neur otransmission, cell adhesion, and neural plasticity. Experiments have shown that normal neural activity is associated with changes in extracellular ca lcium, which has motivated recent computational work that employs such fluc tuations in an information-bearing role. This possibility suggests that a n ew style of computing is taking place in the mammalian brain in addition to current 'circuit' models that use only neurons and connections. Previous c omputational models of rapid external calcium changes used only rough appro ximations of calcium channel dynamics to compute the expected calcium decre ments in the extracellular space. Using realistic calcium channel models, e xperimentally measured back-propagating action potentials, and a model of t he extracellular space, we computed the fluctuations in external calcium th at accrue during neural activity. In this realistic setting, we showed that rapid, significant changes in local external calcium can occur when dendri tes are invaded by back-propagating spikes, even in the presence of an extr acellular calcium buffer. We further showed how different geometric arrange ments of calcium channels or dendrites prolong or amplify these fluctuation s. Finally, we computed the influence of experimentally measured synaptic i nput on peridendritic calcium fluctuations. Remarkably, appropriately timed synaptic input can amplify significantly the decrement in external calcium . The model shows that the extracellular space and the calcium channels tha t access it provide a medium that naturally integrates coincident spike act ivity from different dendrites that intersect the same tissue volume.