Viral-mediated expression of a constitutively active form of CREB in the dentate gyrus does not induce abnormally enduring fear memory
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.
SourceAvailable from: Johannes Felsenberg[Show abstract] [Hide abstract]
ABSTRACT: In classical conditioning a predictive relationship between a neutral stimulus (conditioned stimulus; CS) and a meaningful stimulus (unconditioned stimulus; US) is learned when the CS precedes the US. In backward conditioning the sequence of the stimuli is reversed. In this situation animals might learn that the CS signals the end or the absence of the US. In honeybees 30 min and 24 h following backward conditioning a memory for the excitatory and inhibitory properties of the CS could be retrieved, but it remains unclear whether a late long-term memory is formed that can be retrieved 72 h following backward conditioning. Here we examine this question by studying late long-term memory formation in forward and backward conditioning of the proboscis extension response (PER). We report a difference in the stability of memory formed upon forward and backward conditioning with the same number of conditioning trials. We demonstrate a transcription-dependent memory 72 h after forward conditioning but do not observe a 72 h memory after backward conditioning. Moreover we find that protein degradation is differentially involved in memory formation following these two conditioning protocols. We report differences in the level of a transcription factor, the cAMP response element binding protein (CREB) known to induce transcription underlying long-term memory formation, following forward and backward conditioning. Our results suggest that these alterations in CREB levels might be regulated by the proteasome. We propose that the differences observed are due to the sequence of stimulus presentation between forward and backward conditioning and not to differences in the strength of the association of both stimuli.Frontiers in Behavioral Neuroscience 03/2015; 9(91). DOI:10.3389/fnbeh.2015.00091 · 4.16 Impact Factor
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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. DOI:10.1007/s12035-011-8209-x · 5.29 Impact Factor
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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; 115. DOI:10.1016/j.nlm.2014.08.010 · 4.04 Impact Factor