Endogenous electric currents might guide rostral migration of neuroblasts

Abstract

Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 lA/cm 2 , average field strength of B3 mV/mm) along the rostral migration path in adult mouse brain. Electric fields of similar strength direct migration of neuroblasts from the SVZ in culture and in brain slices. The purinergic receptor P2Y1 mediates this migration. The results indicate that naturally occurring electric currents serve as a new guidance mechanism for rostral neuronal migration.

Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells

“…Nevertheless, our results highlight the novel role of HS as an EF sensor during galvanotaxis and provide direct evidence in support of the electrophoretic galvanotaxis model. These findings could have broad implications in many physiological events as cells ubiquitously express HS and small EFs have been associated with neural development (Burr, 1941;Cao et al, 2013), wound healing (Zhao et al, 2006) and metastatic disease (Mycielska and Djamgoz, 2004). Understanding how endogenous EFs could guide cell migration and how an applied EF could potentially be leveraged to modulate this process provide a rationale for new therapeutics.…”

“…The brain exhibits one of the highest electrical activities amongst all organs in the body; electric fields in the brain are not an epiphenomenon but actively regulate cellular functions. For example, the endogenous electric field between the subventricular zone and olfactory bulb was found to direct the migration of neuroblasts and guide the migration of neural precursor cells along the rostral migratory stream (Cao et al, 2013). Furthermore, increased electrical activity stimulated by optogenetics accelerates glioma growth in vivo (Venkatesh et al, 2015).…”

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS

“…Spatio-temporal gradients of V mem across groups of cells serve as instructive bioelectric signals (Levin, 2013b, Levin, 2014b, Mustard and Levin, 2014. Such patterns of resting potential within living tissues (bioelectric signals) have been studied in the context of their roles in cell migration and wound healing (Cao et al, 2013, Jaffe, 1979, McCaig et al, 2005, Richard B. Borgens, 1989, Zhao et al, 2006 and have long been proposed to direct growth and form in vivo (Burr, 1932). Bioelectric signals are implicated in vertebrate appendage regeneration , Tseng et al, 2010, cancer initiation and metastasis (Binggeli and Weinstein, 1986b, Blackiston et al, 2011, Brackenbury, 2012, Chernet and Levin, 2013b, Lobikin et al, 2012b, left-right patterning (Aw et al, 2008, Aw et al, 2010, Levin et al, 2002, planarian head induction (Beane et al, 2011, Beane et al, 2013, Marsh and Beams, 1947, and eye and brain formation (Nuckels et al, 2009, Pai et al, 2015, Pai et al, 2012a, Pai et al, 2012b.…”

Therapeutic Application of Electric Fields in the Injured Nervous System

“…Interestingly, Cao and colleagues showed in a recent study that endogenous electric signals could regulate the directional migration of neuroblast cells toward the rostral migratory stream in vivo. 48 This suggests exogenous EFs may modulate neural stem cell behavior. Indeed, we and other labs proved that neural stem cells can be controlled to recruit directionally in an applied physiological level of EF, 49,50 and our lab has shown is it possible to regulate such cellular response in a three-dimensional organotypic spinal cord slice culture model with electric stimulation, 50 which suggests great potential for the use of exogenous EFs after grafting in vivo, as an innovative approach to optimize the stem cell based therapy in treating nervous system injuries.…”