title: Chronaxie Measurements in Patterned Neuronal Cultures from Rat Hippocampus.
abstract: Excitation of neurons by an externally induced electric field is a long standing question that has recently attracted attention due to its relevance in novel clinical intervention systems for the brain. Here we use patterned quasi one-dimensional neuronal cultures from rat hippocampus, exploiting the alignment of axons along the linear patterned culture to separate the contribution of dendrites to the excitation of the neuron from that of axons. Network disconnection by channel blockers, along with rotation of the electric field direction, allows the derivation of strength-duration (SD) curves that characterize the statistical ensemble of a population of cells. SD curves with the electric field aligned either parallel or perpendicular to the axons yield the chronaxie and rheobase of axons and dendrites respectively, and these differ considerably. Dendritic chronaxie is measured to be about 1 ms, while that of axons is on the order of 0.1 ms. Axons are thus more excitable at short time scales, but at longer time scales dendrites are more easily excited. We complement these studies with experiments on fully connected cultures. An explanation for the chronaxie of dendrites is found in the numerical simulations of passive, realistically structured dendritic trees under external stimulation. The much shorter chronaxie of axons is not captured in the passive model and may be related to active processes. The lower rheobase of dendrites at longer durations can improve brain stimulation protocols, since in the brain dendrites are less specifically oriented than axonal bundles, and the requirement for precise directional stimulation may be circumvented by using longer duration fields.
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Stern
authors.affiliation: Department of Non-linear Dynamics, Max Planck Institute for Dynamics and Self-Organization and Bernstein Group 'Biophysics of Neural Computation', Göttingen, Germany.
authors.forename: Andres
authors.initials: A
authors.lastname: Agudelo-Toro
authors.affiliation: Department of Physics and School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Assaf
authors.initials: A
authors.lastname: Rotem
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Elisha
authors.initials: E
authors.lastname: Moses
authors.affiliation: Department of Non-linear Dynamics, Max Planck Institute for Dynamics and Self-Organization and Bernstein Group 'Biophysics of Neural Computation', Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Neef
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002907:Chronaxy / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D026902:Potassium Channel Blockers / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D015761:4-Aminopyridine; C006749:bicuculline methochloride; D002118:Calcium; D001640:Bicuculline