Upregulation of cAMP response element-mediated gene expression during experience-dependent plasticity in adult neocortex

Gene transcription is thought to be essential for memory consolidation and long-lasting changes in synaptic function. In particular, the signal transd uction pathways that activate the transcription factor cAMP response elemen t binding protein (CREB) have been implicated in the process of synaptic po tentiation. To study the involvement of this pathway in neocortical plastic ity within the barrel cortex, we have used a strain of mice carrying a LacZ reporter gene with six cAMP response elements (CREs) upstream of a minimal promoter. Removal of all but one facial whisker results in the expansion o f the spared whisker's functional representation within somatosensory corte x. Under the same conditions of whisker deprivation, we observed a strong ( eightfold compared with baseline) and highly place-specific upregulation of CRE-mediated gene transcription in layer IV of the spared whisker barrel. Reporter gene upregulation occurred rapidly after deprivation (16 hr) and w as only observed under experimental conditions capable of inducing whisker response potentiation. LacZ expression in layer IV was accompanied by an in crease in responsiveness of a subpopulation of layers II/III cells to spare d whisker stimulation as determined by in vivo single-unit recording. Given that CREB is involved in the expression of plasticity in superficial layer s (Glazewski et al., 1999), and yet CRE-mediated gene expression occurs in layer IV, it is likely that the molecular events initiating plasticity occu r presynaptically to the cells that exhibit changes in their receptive fiel d properties.