Specific regulation of immediate early genes by patterned neuronal activity

Abstract

Electrical activity shapes development of the nervous system, presumably in part by regulating gene expression. A set of regulatory genes, immediate early genes (IEGs), which are responsive to a number of extrinsic cellular stimuli have been proposed to play a role in coupling such activity to gene expression. Using a semiquantitative polymerase chain reaction assay, we show that in dissociated mouse dorsal root ganglion neurons the expression of two IEGs, c-fos and nur/77, is differentially sensitive to patterns of electrical stimulation. Differences in c-fos activation did not correlate with the peak intracellular calcium [Ca⁺⁺]i produced by the different stimulation patterns or with residual [Ca⁺⁺]i following stimulation. However, the net increase in [Ca⁺⁺]i (calcium time integral) was greater for the pulsed stimulus that activated c-fos (6 impulses/min), compared to the ineffective stimulus (12 impulses/2 min). This system of genes seems suited to mediating the coupling between electrical activity and other functional genes.