Hippocampal CRE-mediated gene expression is required for contextual memory formation

Athos, Jaime; Impey, Soren; Pineda, Victor V.; Chen, Xi; Storm, Daniel R.

doi:10.1038/nn951

Cited by 137 publications

(117 citation statements)

References 15 publications

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“…Furthermore, results similar to those obtained with antisense sequences have been reported using several other approaches including temporally-regulated expression of dominant negative molecules (Chen, Muzzio, Malleret, Bartsch, Verbitsky, Pavlidis, Yonan, Vronskaya, Grody, Cepeda, Gilliam, & Kandel, 2003;Yin et al, 1994), interfering decoys (e.g. Alberini et al, 1994;Athos, Impey, Pineda, Chen, & Storm, 2002;Dash, Hochner, & Kandel, 1990;Dash, Orsi, & Moore, 2005;Freudenthal, Boccia, Acosta, Blake, Merlo, Baratti, & Romano, 2005) or blocking antibodies (Alberini et al, 1994;Bartsch, Casaio, Karl, Serodio, & Kandel, 1998). Given the consistency of the findings with different molecular blocking approaches and the high number of different molecules targeted, it is reasonable to conclude that it is the blocking effect that unravels the biosynthestic molecular requirements for memory formation.…”

Section: The Role Of Protein Synthesis In Long-term Synaptic Plasticisupporting

confidence: 68%

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

Alberini

2008

Neurobiology of Learning and Memory

157

111

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Despite the fact that extensive evidence supports the view that phases of de novo protein synthesis are necessary for memory formation and maintenance, doubts are still raised. Skeptics generally argue that amnesia and the disruption of long-term synaptic plasticity are caused by "non-specific effects" of the reagents or approaches used to disrupt protein synthesis. This paper attempts to clarify some of these issues by reviewing, discussing and providing results addressing some of the major critiques that argue against the idea that de novo protein synthesis is necessary for the stabilization of long-term memory.

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Section: The Role Of Protein Synthesis In Long-term Synaptic Plasticisupporting

confidence: 68%

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

Alberini

2008

Neurobiology of Learning and Memory

157

111

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“…There is also evidence that the memory extinction signaling pathways are different from those involved in memory consolidation (Lin et al, 2003;Szapiro et al, 2002;Fischer et al, 2004). Our data demonstrate through a novel experimental procedure of subchronic PDE inhibition the pivotal role of hippocampal CREB activation in memory consolidation (Bourtchuladze et al, 1994;Impey et al, 1998;Taubenfeld et al, 1999Taubenfeld et al, , 2001aAthos et al, 2002). At the same time, our results do not support a direct role of CREB activation in memory extinction, as the slowing down of the extinction process occurred in our model when Rolipram was not released any more.…”

Section: Discussionsupporting

confidence: 52%

Subchronic Rolipram Delivery Activates Hippocampal CREB and Arc, Enhances Retention and Slows Down Extinction of Conditioned Fear

Monti

Berteotti

Contestabile

2005

Neuropsychopharmacol

102

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Rolipram, a type IV-specific phosphodiesterase inhibitor, is known to improve memory under various learning tasks. Moreover, Rolipram treatments have been shown to increase expression and phosphorylation of a key factor for hippocampal memory consolidation, the cAMP-dependent response element-binding protein, CREB. However, the exact correlation between hippocampal CREB phosphorylation and memory improvement induced by Rolipram has not yet been determined in a CREB-dependent type of hippocampal-related learning in normogenic, intact rodents. Here, we report that subchronic Rolipram delivery by using osmotic minipumps increased the basal rat hippocampal expression and phosphorylation of CREB, as well as the expression of the cAMPdependent, memory-related protein, Arc. In parallel, the same treatment improved memory consolidation of conditioned fear. Furthermore, the increase of CREB phosphorylation and Arc expression consequent to the learning experience was enhanced in Rolipram-treated rats, compared to controls. By evaluating the time course of memory extinction over 10 days after the initial learning test, we also observed significant slowing down of the memory extinction rate in Rolipram-treated rats. This effect could be attributed to CREB phosphorylation and memory having been initially higher, as osmotic minipumps stopped to release Rolipram the first day after the initial learning test. Our data define the conditions through which the pharmacological manipulation of hippocampal CREB expression and activation result in memory amelioration in normogenic, intact animals. These results are relevant for the study of molecular correlates of memory, and may also be important in view of the efforts to design new pharmacological treatments, targeting the CREB pathway and leading to enhancement of learning and memory, even in the absence of patent neuropathology.

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“…Atomoxetine could reverse behavioral deficits that result from such alterations by stimulating those same cell-signaling cascades. For example, extracellular-regulated kinase (ERK) is critically involved in contextual fear conditioning (see Adams and Sweatt (2002) and Sweatt (2004) for reviews), and cAMP response element binding protein (CREB), one of the downstream targets of ERK (Abel and Kandel, 1998;Abel and Lattal, 2001;Athos et al, 2002;Bourtchuladze et al, 1994), is also critically involved in contextual fear conditioning (Athos et al, 2002;Bourtchuladze et al, 1994). Recent research indicates that chronic nicotine administration alters both ERK and CREB activation (Brunzell et al, 2003), and nicotine withdrawal also alters CREB activation (Brunzell et al, 2003;Pandey et al, 2001;Pluzarev and Pandey, 2004).…”

Section: Discussionmentioning

confidence: 99%

Atomoxetine Reverses Nicotine Withdrawal-Associated Deficits in Contextual Fear Conditioning

Davis

Gould

2007

Neuropsychopharmacol

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Recent evidence suggests that the cognitive symptoms of nicotine withdrawal and the cognitive symptoms of attention deficit hyperactivity disorder (ADHD) may share neural correlates. Thus, therapeutics that ameliorate ADHD symptoms may also ameliorate nicotine-withdrawal symptoms. The present research tested this hypothesis in an animal model of nicotine withdrawal-associated cognitive deficits using atomoxetine, a norepinephrine reuptake inhibitor that is approved by the FDA to treat the symptoms of ADHD. C57BL/6 mice were prepared with osmotic minipumps that administered 6.3 mg/kg/day of nicotine or saline, and the minipumps were removed after 12 days of continuous treatment. Twenty-four hours later, mice were trained in delay fear conditioning using two paired presentations of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus. Testing for freezing in response to the training context and for freezing in response to the CS occurred the next day. Nicotine-withdrawn mice and their saline-treated counterparts received either saline or atomoxetine before training and the context test. Consistent with previous research, the results indicate that mice withdrawn from chronic nicotine demonstrated lower levels of contextual fear conditioning than mice that were not withdrawn from chronic nicotine. Atomoxetine dose-dependently reversed the deficit, suggesting that nicotine withdrawal may be associated with changes in noradrenergic function, acetycholinergic function, and/or with changes in cell signaling cascades that are activated by both nicotine and norepinephrine. These data suggest that atomoxetine may be efficacious for treating nicotine withdrawalassociated cognitive deficits that promote relapse in abstinent smokers.

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Hippocampal CRE-mediated gene expression is required for contextual memory formation

Cited by 137 publications

References 15 publications

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

The role of protein synthesis during the labile phases of memory: Revisiting the skepticism

Subchronic Rolipram Delivery Activates Hippocampal CREB and Arc, Enhances Retention and Slows Down Extinction of Conditioned Fear

Atomoxetine Reverses Nicotine Withdrawal-Associated Deficits in Contextual Fear Conditioning

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