CRE-Mediated Gene Transcription in Neocortical Neuronal Plasticity during the Developmental Critical Period

Abstract

Neuronal activity-dependent processes are believed to mediate the formation of synaptic connections during neocortical development, but the underlying intracellular mechanisms are not known. In the visual system, altering the pattern of visually driven neuronal activity by monocular deprivation induces cortical synaptic rearrangement during a postnatal developmental window, the critical period. Here, using transgenic mice carrying a CRE-lacZ reporter, we demonstrate that a calcium- and cAMP-regulated signaling pathway is activated following monocular deprivation. We find that monocular deprivation leads to an induction of CRE-mediated lacZ expression in the visual cortex preceding the onset of physiologic plasticity, and this induction is dramatically downregulated following the end of the critical period. These results suggest that CRE-dependent coordinate regulation of a network of genes may control physiologic plasticity during postnatal neocortical development.

Acceleration of Visual System Development by Environmental Enrichment

“…Genotyping was performed by PCR. CREmediated gene expression was revealed by means of X-gal histochemistry (Impey et al, 1996;Pham et al, 1999;Barth et al, 2000). After the mice were killed (between 8:30 and 9:30 A.M.), brains were dissected out and submerged in ice-cold fixative (3% paraformaldehyde, 0.1 M PB) for 3 hr.…”

“…An important hub in the development and plasticity of sensory systems and in particular of the visual system is the cAMP/ CREB pathway (Impey et al, 1996;Pham et al, 1999;Barth et al, 2000;Mower et al, 2002;Cancedda et al, 2003). To investigate the involvement of this system in mediating the effects of environmental enrichment on visual system development, we used transgenic mice that carry the LacZ reporter gene under the control of the CRE promoter (Impey et al, 1996).…”

“…One of the targets of BDNF signaling is the activation of cAMP response element (CRE)-binding protein (CREB), a transcription factor with a well established role in development and plasticity of the visual system either at cortical level (Pham et al, 1999;Cancedda et al, 2003) or, more precociously, at geniculate level (Pham et al, 2001). Enriched environment increases CREB expression and phosphorylation in the hippocampus of adult animals (Williams et al, 2001), but it is not known whether it regulates CRE-mediated gene expression in the developing visual cortex.…”

Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells

“…The nuclear transcription factor cAMP response elementbinding protein (CREB) is a major downstream target of ERK1/2 signaling that contributes to neuronal differentiation in PC12 cells (Heasley et al, 1991;Ginty et al, 1994) and to brain neuroplasticity (Impey et al, 1998bSgambato et al, 1998;Pham et al, 1999) and neuronal survival (Bonni et al, 1999;Riccio et al, 1999;Nakagawa et al, 2002). CREB binds constitutively to the specific DNA motif, 5Ј-TGACGTCA-3Ј known as CRE, and its activity is triggered by phosphorylation in Ser133 (González and Montminy, 1989).…”

Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance

“…Furthermore, robust CREB phosphorylation and cAMP-response elementreporter gene expression are detected in cortical neurons during developmental plasticity (95) and in hippocampal neurons in response to both LTP-inducing stimuli and memory-training tasks (96,97) . Furthermore, CREB is known to be a critical transcription factor linking the actions of neurotrophins such as brain-derived neurotrophic factor (BDNF) to neuronal survival, differentiation and synaptic function (98,99) .…”