cAMP response element-binding protein is a primary hub of activity-driven neuronal gene expression.

Long-lasting forms of neuronal plasticity require de novo gene expression, but relatively little is known about the events that occur genome-wide in response to activity in a neuronal network. Here, we unveil the gene expression programs initiated in mouse hippocampal neurons in response to different stimuli and explore the contribution of four prominent plasticity-related transcription factors (CREB, SRF, EGR1, and FOS) to these programs. Our study provides a comprehensive view of the intricate genetic networks and interactions elicited by neuronal stimulation identifying hundreds of novel downstream targets, including novel stimulus-associated miRNAs and candidate genes that may be differentially regulated at the exon/promoter level.

CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.

The epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CREB-binding protein (CBP), a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioural adaptations to environmental enrichment (EE). Morphological and behavioural analyses demonstrated that EE ameliorates deficits associated to CBP deficiency.

Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability.

Rubinstein-Taybi syndrome (RSTS) is an inheritable disease associated with mutations in the gene encoding the CREB (cAMP response element-binding protein)-binding protein (CBP) and characterized by growth impairment, learning disabilities, and distinctive facial and skeletal features. Studies in mouse models for RSTS first suggested a direct role for CBP and histone acetylation in cognition and memory. Here, we took advantage of the genetic tools for generating mice in which the CBP gene is specifically deleted in postmitotic principal neurons of the forebrain to investigate the consequences of the loss of CBP in the adult brain.

Inhibition of cAMP responsive element binding protein in striatal neurons enhances approach and avoidance responses toward morphine--and morphine withdrawal-related cues.

To investigate the role of cAMP responsive element binding protein (CREB)-dependent gene expression in morphine induced behaviors, we examined bitransgenic mice expressing a dominant and strong inhibitor of the CREB family of transcription factors, A-CREB, in striatal neurons in a regulatable manner. The expression of A-CREB in the striatum enhanced both morphine-induced conditioned place preference and morphine withdrawal-induced conditioned place avoidance. Our experiments thereby support a role for CREB in striatal neurons regulating approach and avoidance responses toward drug-related cues.