A cell culture preparation equipped with stimulating electrodes was us
ed to investigate whether action potential activity can influence myel
ination of mouse dorsal root ganglia axons by Schwann cells. Myelinati
on was reduced to one-third of normal by low-frequency impulse activit
y (0.1 Hz), but higher-frequency stimulation (1 Hz) had no effect. The
number of Schwann cells and the ultrastructure of compact myelin were
not affected. The frequency of stimulation that inhibited myelination
decreased expression of the cell adhesion molecule L1, and stimulatio
n under conditions that prevented the reduction in L1 blocked the effe
cts on myelination. This link between myelination and functional activ
ity in the axon at specific frequencies that change axonal expression
of L1 could have important consequences for the structural and functio
nal relationship of myelinating axons.