Current-Distance Relations for Microelectrode Stimulation of Pyramidal Cells Cornelia Wenger, Liliana Paredes, and Frank Rattay Vienna University of Technology, Vienna, Austria Abstract: 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 enlight- ened the spike initiation sites for extracellular cortical microstimulation and revealed insights into dendritic exci- tation patterns. Surprisingly low dendritic threshold values for cathodic stimulation were detected, that is, 3.3 mA for a 0.4-mm diameter fiber excited with a 100-ms pulse in 4-mm distance. However, according to the activating func- tion 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. Key Words: Micro- electrode stimulation—Pyramidal cell—Dendrite stimu- lation—Computer simulation—Multicompartment model —Current-distance relation—Activating function— Functional electrical stimulation. Modern techniques like patch clamp, immu- nochemistry, and tracing methods develop rapidly and constantly reveal detailed recording data causing deficiencies in theoretical investigations. Therefore, the excitation pattern along the whole neural axis has to be examined to understand the underlying mecha- nism when low current pulses are applied for cortical stimulation. Consistent with previous work (1) our results confirmed the myelinated axons to be the most sensitive elements for external stimulation, fol- lowed by non-myelinaned fibers, whereas the soma is rather difficult to stimulate. A crucial question concerns the spike generator site. New findings on the distribution of voltage sensi- tive ion channels revealed the dendrites as possible candidates as they act as independent processing units (2). Although the inverse recruitment order, causing plenty of problems in functional electrical stimulation (FES), states that thick fibers are more excitable, our findings indicate that thin dendrites can be more easily stimulated under certain circumstances. The presented results for dendritic spike initiation are not in accordance with a quadratic current- distance relation that is assumed by many authors without defining which part of the neuron has been examined (3). Accounting for the fact that most theo- retical investigations focus on simulation of intra- cellular stimulation (4), we applied the activating function concept to an L5 (layer 5) pyramid cell, a typical cortical neuron, to analyze the current dis- tance relations. MATERIALS AND METHODS The activation function concept has been con- nected with a multicompartment model to test current-distance relations along the neural axis. We doi:10.1111/j.1525-1594.2011.01224.x Received December 2010. Address correspondence and reprint requests to Dr. Frank Rattay, Institute of Analysis and Scientific Computing, Vienna University of Technology, Wiedner Hauptstrasse 8-10, A-1040 Wien, Austria. E-mail: frank.rattay@tuwien.ac.at Presented in part at the 10th Vienna International Workshop on Functional Electrical Stimulation and 15th IFESS Annual Confer- ence held September 8–12, 2010 in Vienna, Austria. Artificial Organs 35(3):263–266, Wiley Periodicals, Inc. © 2011, Copyright the Authors Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. 263