Orientation of neurite growth by extracellular electric fields

Abstract

Extracellularly applied steady electric fields of 0.1 to 10 V/cm were found to have marked effects on the neurite growth of single dissociated Xenopus neurons in culture: (1) neurites facing the cathode showed accelerated growth, while the growth of those facing the anode was reduced. Neurites growing relatively perpendicular to the field axis were prompted to curve toward the cathode. (2) More neurites appeared to be initiate from the cathodal side of the cell. (3) The number of neurite-bearing neurons per culture and the average neurite length were increased. These effects are absent in cultures treated with electric fields of similar strength but alternating polarity and cannot be attributed either to a gradient of extracellular diffusible substances or to the flow of culture medium produced by the field. The field effects are reversible: (1) removal of the electric field resulted in the loss of neurite orientation in a few hours and (2) reversal of the polarity of the electric field led to a rapid reversal in the neurite orientation. To determine the cellular loci of these field effects, we treated the neurons with a number of pharmacological agents or altered their ionic environments. Incubation with concanavalin A (Con A) was found to abolish these filed effects completely. Since the binding of Con A to the neuronal surface was shown to prevent field-induced accumulation of the Con A receptors toward the cathodal side of these neurons, our finding is accumulation of the Con A receptors toward the cathodal side of these neurons, our finding is consistent with the notion that cathodal accumulation of growth-controlling surface glycoproteins by the field is the underlying mechanism of the field-induced orientation of neurite growth toward the cathode.

Rapid sprouting of filopodia in nerve terminals of chromaffin cells, PC12 cells, and dorsal root neurons induced by electrical stimulation

“…It has been suggested that electrical activity might influence the morphological characteristics and functional connectivity in the nervous system during development and in neuroplastic events. In fact, electrical activity influences various neuronal properties like synthesis of neurotransmitters (Walicke et al, 1977;Ip and Zigmond, 1984) expression of neurotransmitter receptors (Lomo and Rosenthal, 1972;Zigmond and Bowers, 198 I), the rate and direction of neurite outgrowth (Borgens et al, 1981;Pate1 and Poo, 1982;Cohan and Kater, 1986) formation and pattern of synaptic connections (Changeux and Danchin, 1976;Archer et al, 1982) and sprouting at the neuromuscular junction (Brown and Ironton, 1977;Brown et al, 198 1). Receptor-mediated changes in the morphology and the activity of the neuronal growth cone have been shown to be induced by serotonin (Haydon et al, 1984) and nerve growth factor (NGF) (Connolly et al, 1987).…”

Single session of brief electrical stimulation immediately following crush injury enhances functional recovery of rat facial nerve

“…Our initial studies investigated the therapeutic potential of ES in nerve regeneration following a rat facial nerve crush injury because of ES's enhancing effects on the morphological and functional properties of neurons [1][2][3][4]. In these studies, daily, low-frequency ES hastened the onset of recovery of the eye blink reflex by reducing the initial delay in sprout formation rather than by increasing the rate of axonal regeneration, indicating that ES acts primarily on events in the early stages of recovery [5][6][7].…”

“…Applying electrical stimulation (ES) has been shown to affect morphological and functional properties of neurons such as nerve branching, rate and orientation of neurite growth, rapid sprouting, and guidance during axon regeneration [1][2][3][4]. Therefore, ES has been explored as a therapeutic strategy for improving the outcome of peripheral nerve injury.…”

Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview

“…However, after a lag period of 30 min following the exposure to voltage gradient, the neurites facing the anode start to regress as if being repelled by the anodal electrode. Further clarification on the response of applied Direct Current (DC) voltages on single nerve fibres was shown by Hinkle et al [40] and Patel & Poo [64]. They observed that the neurites that were parallel to the field grow towards the cathode, while the ones that were perpendicular to the electric field turned in order to grow towards the cathode.…”

“…In the absence of such guidance, the axonal growth in the CNS results in a haphazard sprouting. Various researchers studying the effects of weakly applied electric fields on the innately regenerating axons have suggested that exogenously applied weak electric fields around the lesioned axons have a role to play in facilitating axonal regeneration, possibly by providing neurotropic guidance to the growing axons [6,56,57,64].…”