Which elements of the mammalian central nervous system are excited by low current stimulation with microelectrodes?

Low current cortex stimulation produces a sparse and distributed set of activated cells often with distances of several hundred micrometers between cell bodies and the microelectrode. A modeling study based on recently measured densities of high threshold sodium channels Nav1.2 in dendrites and soma and low threshold sodium channels Nav1.6 in the axon shall identify spike initiation sites including a discussion on dendritic spikes. Varying excitability along the neural axis has been observed while studying different electrode positions and configurations. Although the axon initial segment (AIS) and nodes of Ranvier are most excitable, many thin axons and dendrites which are likely to be close to the electrode in the densely packed cortical regions are also proper candidates for spike initiation sites. Cathodic threshold ratio for thin axons and dendrites is about 1:3, whereas 0.2 μm diameter axons passing the electrode tip in 10 μm distance can be activated by 100 μs pulses with 2.6 μA. Direct cathodic excitation of dendrites requires a minimum electrode-fiber distance, which increases with dendrite diameter. Therefore thin dendrites can profit from the stronger electrical field close to the electrode but low current stimulation cannot activate large diameter dendrites, contrary to the inverse recruitment order known from peripheral nerve stimulation. When local depolarization fails to generate a dendritic spike, stimulation is possible via intracellular current flow that initiates an action potential, for example 200 μm distant in the low threshold AIS or in certain cases at the distal dendrite ending. Beside these exceptions, spike initiation site for cathodic low current stimulation appears rather close to the electrode.