Small applied electric fields guide migration of hippocampal neurons.
Effectively directed neuron migration is critical for development and repair in the central nervous system (CNS). Endogenous electric fields (EFs) are widespread in developing and regenerating tissues and regulate a variety of cell behaviors including directed cell migration. Electrically-directed neuronal migration has not been tested previously and we show that an applied EF directs migration of hippocampal neurons toward the cathode at a field strength of 120 mV/mm, close to the physiological range. Reversal of the field polarity reversed the direction of neuron migration. Neuron migration from an explant also was directed by an applied EF. Mechanistically, EF-guided migration was transduced by activation of the second messenger molecules ROCK (Rho-associated protein kinase) and PI3 kinase (phosphoinositide-3 kinase) since their pharmacological inhibition decreased the directedness and speed of neuron migration. This work demonstrates that rat hippocampal neurons respond to applied EFs with directional migration and raises the possibility that EFs may be used as a cue to direct neuronal migration in novel strategies to repair the CNS.
Yao
Li
L
School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Shanley
Lynne
L
McCaig
Colin
C
Zhao
Min
M
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004560:Electricity; D004566:Electrodes; D004791:Enzyme Inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein