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Epigenetic modification of chromatin has been proposed to translate environmental stimuli into persistent “cellular memories.” Recent studies suggest that epigenetic pathways regulate long-term behavioral adaptation in the nervous system. In this issue of Neuron, Renthal et al. utilize genetic manipulations of HDAC5 to provide strong evidence for a role for histone acetylation in the behavioral response...
microRNAs (miRNAs) are a class of small, noncoding RNAs that regulate the stability or translation of mRNA transcripts. Although recent work has implicated miRNAs in development and in disease, the expression and function of miRNAs in the adult mammalian nervous system have not been extensively characterized. Here, we examine the role of two brain-specific miRNAs, miR-219 and miR-132, in modulating...
Members of the Wnt signaling family are important mediators of numerous developmental events, including activity-dependent dendrite development, but the pathways regulating expression and secretion of Wnt in response to neuronal activity are poorly defined. Here, we identify an NMDA receptor-mediated, Ca 2+ -dependent signaling pathway that couples neuronal activity to dendritic arborization...
Activity-regulated transcription has been implicated in adaptive plasticity in the CNS. In many instances, this plasticity depends upon the transcription factor CREB. Precisely how neuronal activity regulates CREB remains unclear. To address this issue, we examined the phosphorylation state of components of the CREB transcriptional pathway. We show that NMDA activates transcription of CREB-responsive...
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,...
Although Ca2+-stimulated cAMP response element binding protein– (CREB-) dependent transcription has been implicated in growth, differentiation, and neuroplasticity, mechanisms for Ca2+-activated transcription have not been defined. Here, we report that extracellular signal–related protein kinase (ERK) signaling is obligatory for Ca2+-stimulated transcription in PC12 cells and hippocampal neurons....
Acute desensitization of olfactory signaling is a critical property of the olfactory system that allows animals to detect and respond to odorants. Correspondingly, an important feature of odorant-stimulated cAMP increases is their transient nature, a phenomenon that may be attributable to the unique regulatory properties of the olfactory adenylyl cyclase (AC3). AC3 is stimulated by receptor activation...
Gene expression regulated by the cAMP response element (CRE) has been implicated in synaptic plasticity and long-term memory. It has been proposed that CRE-mediated gene expression is stimulated by signals that induce long-term potentiation (LTP). To test this hypothesis, we made mice transgenic for a CRE-regulated reporter construct. We focused on long-lasting long-term potentiation (L-LTP), because...
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