Shock tactics for new neurons -- 14 March 2001

Electricity may trigger nerve growth.

Electric currents could help rewire injured brains.

Like jump-starting a car, one way to regrow nerves after injury may be to shock them. A study released this month shows that electric currents can spark growth in embryonic nerve cells, raising hopes that the same might be true of adult neurons¹.

Nerve cells in the developing embryo have to find their way over long distances through the spinal cord and brain. A growing nerve tip, or 'growth cone', encounters patches of guidance molecules. These tell it which direction to take.

But evidence is mounting that electrical signals conducted by the nerve cells also help them to choose the right pathway. "We suspected that electrical activity may influence guidance behaviour too," says Mu-ming Poo at the University of California in Berkeley. So Poo's team looked at an animal of very little brain: the frog.

The group sent short electric shocks through cultures of sprouting frog neurons. When the stimulated neurons came to a molecular signpost telling them to change direction, they behaved completely differently to unstimulated cells. Signals that normally have no effect prompted growth; signals which normally drive neurons back lured them forward.

"It [electrical stimulation] can alter steering of a growth cone," agrees Christine Holt of the University of Cambridge, who works on neuron guidance in the frog brain. "And, interestingly, it can help stimulate growth."

But Holt is not convinced that neurons use electrical impulses to navigate during normal development. Before they're fully wired up, growing neurons show only low levels of spontaneous electrical activity. "We still don't know if this is important in guiding them," she says.

Electrical stimulation increases the levels of a critical signalling molecule in the cell called cyclic AMP (cAMP), which determines how the growth cone acts. Holt thinks that, during development, growth cones encounter many signals, all of which control the level of cAMP. "Adding electrical activity feeds into this pathway," she believes.

Nevertheless, Poo's results may be important in understanding adult nerve regeneration after injury. Unlike neurons in the embryo, damaged adult neurons do not grow back, partly because certain molecules at the injury site stop growth. Poo thinks that pulses of electricity could be "an effective means of promoting nerve regeneration".

"Increasing cAMP levels can overcome inhibitors to growth," explains Marie Filbin of City University in New York, who works on chemical, rather than electrical, methods of stimulating nerve regeneration in the brain. "Electrical activity is just another mechanism for raising cAMP."

However, electrical stimulation also lowers the levels of a second critical cell signal, cGMP, she says -- and triggering correct nerve growth requires the right levels of both . "Utlimately, I would try both pharmacological and electrical ways to get regeneration," says Filbin.

1. Ming, G., Henley, J., Tessier-Lavigne, M., Song, H. & Poo, M. Electrical activity modulates growth cone guidance by diffusible factors. Neuron 29, 441 - 452 (2001).