Abstract
In neurons, the convergence of multiple intracellular signaling cascades leading to cAMP-responsive element-binding protein (CREB) activation suggests that this transcription factor plays a critical role in integrating different inputs and mediating appropriate neuronal responses. The nature of this transcriptional response depends on both the type and strength of the stimulus and the cellular context. CREB-dependent gene expression has been involved in many different aspects of nervous system function, from embryonic development to neuronal survival, and synaptic, structural, and intrinsic plasticity. Here, we first review the different methodological approaches used to genetically manipulate CREB activity and levels in neurons in vivo in the adult brain, including recombinant viral vectors, mouse transgenesis, and gene-targeting techniques. We then discuss the impact of these approaches on our understanding of CREB’s roles in neuronal plasticity and memory in rodents. Studies combining these genetic approaches with electrophysiology and behavior provide strong evidence that CREB is critically involved in the regulation of synaptic plasticity, intrinsic excitability, and long-term memory formation. These findings pave the way for the development of novel therapeutic strategies to treat memory disorders.
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Acknowledgments
We thank Franck Aguila (IPMC, France) for the design of Fig. 3. The authors also thank Nicole Calakos (Duke University, USA) and Luis M. Valor and other members of the Barco and Marie labs for critical reading of the manuscript. This research was supported by grants from the Spanish Ministry of Science and Innovation BFU2008-00611 (A.B.), CSD2007-00023 (A.B.), and SAF2008-03194-E (part of the coordinated ERA-Net NEURON project Epitherapy) (A.B.); ATIP grant (CNRS) (H.M.); and the French Foundation Plan Alzheimer (H.M.).
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Barco, A., Marie, H. Genetic Approaches to Investigate the Role of CREB in Neuronal Plasticity and Memory. Mol Neurobiol 44, 330–349 (2011). https://doi.org/10.1007/s12035-011-8209-x
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DOI: https://doi.org/10.1007/s12035-011-8209-x