Summary

This chapter described electrical activation of neurons within the central nervous system (CNS). Electrical stimulation is used to study the form and function of the nervous system and as a technique to restore function following disease or injury. Successful application of electrical stimulation to treat nervous system disorders as well as interpretation of the results of stimulation require an understanding of the cellular-level effects of stimulation. Quantitative models provide a means to understand the response of neurons to extracellular stimulation. Further, accurate quantitative models provide powerful design tools that can be used to engineer stimuli that produce a desired response.

The fundamental properties of the excitation of CNS neurons were presented with a focus on what neural elements around the electrode are activated under different conditions. During CNS stimulation, action potentials are initiated in the axons of local cells, even for electrodes positioned over the cell body. The threshold difference between cathodic and anodic stimuli arises due to differences in the mode of activation. Anodic stimuli cause depolarization of the axon and excitation via a "virtual cathode," while cathodic stimuli cause hyperpolarization at the site of excitation and the action potential is initiated during repolarization. The threshold for activation of presynaptic terminals projecting into the region of stimulation is often less than or equal to the threshold for direct excitation of local cells, and indirect effects mediated by synaptic transmission may alter the direct effects of stimulation on the postsynaptic cell. The fundamental understanding provided by this analysis enables the rational design and interpretation of studies and devices employing electrical stimulation of the brain or spinal cord.

Acknowledgments

Research in Dr. Grill's laboratory and preparation of this chapter were supported by NIH Grant R01 NS-40894.

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