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Current-distance relations for microelectrode stimulation of pyramidal cells.

Microelectrodes placed within the densely packed cortical neuronal region are surrounded by many thin processes. Although dendrites are considered to be functionally different to axons, they also possess voltage sensitive membrane channels. Therefore, dendritic regions are suitable candidates for spike initiation sites when stimulated externally, although they demand two to three times higher thresholds in comparison with thin axons. Simulations based upon recently reported distributions of two types of sodium channels and traced pyramidal cell data accompanied by a simplified model structure enlightened the spike initiation sites for extracellular cortical microstimulation and revealed insights into dendritic excitation patterns. Surprisingly low dendritic threshold values for cathodic stimulation were detected, that is, 3.3 µA for a 0.4-µm diameter fiber excited with a 100-µs pulse in 4-µm distance. However, according to the activating function concept the excited region is calculated by 1414*electrode-distance, therefore a minimum electrode-fiber distance is required as sufficient sodium channels are needed to produce enough intracellular current for spike conduction. The minimum distance for dendritic spike initiation increases with diameter and hinders low current stimulation of thick dendrites. This effect is in contrast to the inverse recruitment order known from functional electrical stimulation. Simulations were performed using NEURON and MATLAB.