title: Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.
abstract: Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.
authors.affiliation: Department of Biomedical Engineering, Duke University, 136 Hudson Hall, Box 90281, Durham, NC 27708-0281, USA. warren.grill@duke.edu
authors.forename: Warren M
authors.initials: WM
authors.lastname: Grill
authors.forename: Meredith B
authors.initials: MB
authors.lastname: Cantrell
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Robertson
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D048429:Cell Size; D003198:Computer Simulation; D046690:Deep Brain Stimulation; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D011901:Ranvier's Nodes / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors
chemical_list: D015221:Potassium Channels