Small applied electric fields guide migration of hippocampal neurons

Abstract

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.

Biomaterials for Enhancing Neuronal Repair

“…Differentiation was attributed to the topography facilitating binding between cellular integrins and ligands, which (Xie et al, 2009;Schaub and Gilbert, 2011;Wong et al, 2011;Froeter et al, 2014;Koppes et al, 2014;Lee et al, 2015b). b Electrical References: (Jaffe and Stern, 1979;Patel and Poo, 1982;Hotary and Robinson, 1991;Davenport and McCaig, 1993;Metcalf and Borgens, 1994;Yao et al, 2008Yao et al, , 2009Yao et al, , 2011Graves et al, 2011;Koppes et al, 2014;Kim et al, 2016;Ma et al, 2016). c Mechanical Stiffness References: (Balgude et al, 2001;Discher et al, 2005;Jiang et al, 2010;Keung et al, 2012;Lee et al, 2013;Zhang et al, 2014;Mosley et al, 2017).…”

“…In early development, electric potentials define migration paths of the cells and differentiation, driving the formation of the neural tube Robinson, 1990, 1991;Metcalf and Borgens, 1994;Yao et al, 2008;Ma et al, 2016). Signal transmission in neurons is mediated by ion fluxes across the cell membrane.…”

Electrical dimensions in cell science

“…Newborn rat hippocampal neurons and progenitor neurons from the lateral ganglionic eminence both migrate cathodally and, for rat hippocampal neurons, this requires activation of both PI3K and Rho kinase (ROCK) as signalling elements. The receptor transduction mechanisms upstream of PI3K are unexplored (Yao et al, 2008;Li et al, 2008).…”

Transmembrane voltage potential controls embryonic eye patterning inXenopus laevis

“…They control cell migration (McCaig et al, 2009;Prevarskaya et al, 2010;Yao et al, 2008;Yasuda and Adams, 2010), proliferation (Blackiston et al, 2011) and differentiation (Sundelacruz et al, 2009) in a wide variety of systems. Although epithelial electric fields have been implicated in adult eye wound healing Wang et al, 2005;Zhao et al, 2006), the roles of ion flows in eye development have not been explored.…”