Characterization of the time course of changes of the evoked electrical activity in a model of a chemically-induced neuronal plasticity

BACKGROUND: Neuronal plasticity is initiated by transient elevations of neuronal networks activity leading to changes of synaptic properties and providing the basis for memory and learning [1]. An increase of electrical activity can be caused by electrical stimulation [2] or by pharmacological manipulations: elevation of extracellular K(+ )[3], blockage of inhibitory pathways [4] or by an increase of second messengers intracellular concentrations [5]. Neuronal plasticity is mediated by several biochemical pathways leading to the modulation of synaptic strength, density of ionic channels and morphological changes of neuronal arborisation [6]. On a time scale of a few minutes, neuronal plasticity is mediated by local protein trafficking [7] while, in order to sustain modifications beyond 2–3 h, changes of gene expression are required [8]. FINDINGS: In the present manuscript we analysed the time course of changes of the evoked electrical activity during neuronal plasticity and we correlated it with a transcriptional analysis of the underlying changes of gene expression. Our investigation shows that treatment for 30 min. with the GABA(A )receptor antagonist gabazine (GabT) causes a potentiation of the evoked electrical activity occurring 2–4 hours after GabT and the concomitant up-regulation of 342 genes. Inhibition of the ERK1/2 pathway reduced but did not abolish the potentiation of the evoked response caused by GabT. In fact not all the genes analysed were blocked by ERK1/2 inhibitors. CONCLUSION: These results are in agreement with the notion that neuronal plasticity is mediated by several distinct pathways working in unison.