We tested the possibility that exogenous electrical activity from a piezoelectric substrate could influence neuronal structure in cultured spinal cord neurons. Oscillating electrical fields were delivered to rat neurons via substrates consisting of poly(vinylidene fluoride) film, both in its piezoelectric (PZ) and non-piezoelectric (PV) forms. To induce oscillating electrical fields at the film surfaces, a 50 Hz mechanical vibration was applied. After 4 days of mechano-electrical stimulation, neuronal densities were increased by 115% and neurons grew 79% more neurites, with more than double the branch points, compared with neurons grown on non-stimulated PZ films (p < 0.001). The effects were due to electrical field, because vibration applied to non-PZ films did not increase neurite growth. We conclude that the oscillating electric fields produced from PZ polymer substrates can induce plastic changes in neurons of the central nervous system and herein we show its influence on neurite growth and branching.