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.
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ABSTRACT: Competitive and recreational sport on artificial ice tracks has grown in popularity. For track design one needs knowledge of the expected speed and acceleration of the luge on the ice track. The purpose of this study was to develop an approximate simulation model for luge in order to support the initial design of new ice tracks. Forces considered were weight, drag, friction, and surface reaction force. The trajectory of the luge on the ice track was estimated using a quasi-static force balance and a 1d equation of motion was solved along that trajectory. The drag area and the coefficient of friction for two runs were determined by parameter identification using split times of five sections of the Whistler Olympic ice track. The values obtained agreed with experimental data from ice friction and wind tunnel measurements. To validate the ability of the model to predict speed and accelerations normal to the track surface, a luge was equipped with an accelerometer to record the normal acceleration during the entire run. Simulated and measured normal accelerations agreed well. In a parameter study the vertical drop and the individual turn radii turned out to be the main variables that determine speed and acceleration. Thus the safety of a new ice track is mainly ensured in the planning phase, in which the use of a simulation model similar to this is essential.Journal of biomechanics 12/2010; 44(5):892-6. · 2.66 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. · 5.47 Impact Factor