Viral-mediated expression of a constitutively active form of CREB in the dentate gyrus does not induce abnormally enduring fear memory.

Cell Biology and Neurobiology Institute, C.N.R.-National Research Council, 00143 Rome, Italy.
Behavioural brain research (Impact Factor: 3.22). 09/2011; 222(2):394-6.
Source: PubMed

ABSTRACT Increasing CREB-dependent transcription in dentate gyrus (DG) granule cells in vivo using viral-mediated expression of a constitutively active form of CREB (CREBCA) is sufficient to enhance contextual fear memory but whether this treatment renders memory abnormally enduring is unknown. Here we confirm that over-expressing CREBCA in the DG increases retention of contextual fear conditioning (CFC) and show that this memory decays normally. Specifically, the retention scores of CREBCA mice are significantly higher than those of GFP-infected controls 24h after the conditioning, but match them after a longer exposure session and are still in the same range 48 h later. Our findings provide evidence that boosting selectively CREB activity in the DG promotes the formation of a stronger memory trace but does not increase its resistance to extinguish.

1 Bookmark
  • [Show abstract] [Hide abstract]
    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.
    Molecular Neurobiology 09/2011; 44(3):330-49. · 5.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the field of molecular and cellular neuroscience, it is not a trivial task to see the forest for the trees, where numerous, and seemingly independent, molecules often work in concert to control critical steps of synaptic plasticity and signalling. Here, we will first summarize our current knowledge on essential activity-dependent transcription factors (TFs) such as CREB, MEF2, Npas4 and SRF, then examine how various transcription cofactors (TcoFs) also contribute to defining the transcriptional outputs during learning and memory. This review finally attempts a provisory synthesis that sheds new light on some of the emerging principles of neuronal circuit dynamics that are driven by activity-regulated gene transcription to help better understand the intricate relationship between activity-dependent gene expression and cognitive behavior.
    Neurobiology of Learning and Memory 08/2014; · 4.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transcription factor cAMP response element binding protein (CREB) is a key player in synaptic plasticity and learning. Phosphorylation of CREB induced by neuronal activity leads to gene transcription, a process thought to contribute to memory formation. We have previously reported that increasing CREB activity in glutamatergic CA1 pyramidal neurons or in dentate gyrus (DG) granule cells is sufficient to enhance hippocampal-dependent memory formation. This enhancement correlates with an increase in CA1 glutamatergic synaptic plasticity. However, the effects of increasing CREB activity on DG glutamatergic plasticity have not been investigated. To address this issue, we boosted CREB-dependent transcription in DG granule cells in vivo via viral mediated expression of a constitutively active form of CREB (CREBCA). Using in vitro extracellular field recordings of infected slices, we observed an increase in long-term potentiation (LTP) while short-term plasticity and basic synaptic transmission remained unaffected. These data demonstrate that boosting CREB activity in DG granule cells is sufficient to enhance LTP and suggest that this enhancement participates in the formation of better memories.
    Neuroscience 06/2011; 190:21-6. · 3.33 Impact Factor