Molecular Neurobiology

, Volume 44, Issue 3, pp 330–349

Genetic Approaches to Investigate the Role of CREB in Neuronal Plasticity and Memory



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.


CREB Neuronal plasticity Memory Transgenic mice Virus-mediated expression 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Instituto de Neurociencias de AlicanteUniversidad Miguel Hernández—Consejo Superior de Investigaciones CientíficasAlicanteSpain
  2. 2.Institut de Pharmacologie Moléculaire et Cellulaire, CNRS/UNSA UMR6097ValbonneFrance

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