Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

Gerlai, Robert; Henderson, Jeffrey T.; Roder, John; Jia, Zhenping

doi:10.1016/s0166-4328(98)00002-3

Cited by 96 publications

(69 citation statements)

References 52 publications

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“…Moreover, conflicting findings regarding cocaine-induced place preference in GluR-A knock-out mice have been reported previously (Dong et al, 2004;Mead et al, 2005). The role of the GluR-B subunit in this regard has been less studied thus far, in part because of the multiple behavioral abnormalities displayed by GluR-B knock-out mice (Gerlai et al, 1998;Mead and Stephens, 2003b); however, they also show normal cocaineinduced, but not food-induced, place preference (Mead et al, 2005). Therefore, although there is an increasing interest in the possible role of AMPA receptor subunit composition in drug-seeking behavior (Self and Choi, 2004), this genotypephenotype correlation remains elusive and, indeed, similar consequences in relapsing behavior have been hypothesized after the genetic deletion of different AMPA receptor subunits (Mead and Stephens, 2003a,b).…”

Section: Discussionmentioning

confidence: 99%

Involvement of the AMPA Receptor GluR-C Subunit in Alcohol-Seeking Behavior and Relapse

Sanchis‐Segura¹,

Borchardt²,

Vengeliene³

et al. 2006

J. Neurosci.

123

112

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Craving and relapse are core symptoms of drug addiction and alcoholism. It is suggested that, after chronic drug consumption, longlasting neuroplastic changes within the glutamatergic system are important determinants of addictive behavior. Here, we show that the AMPA type glutamate receptor plays a crucial role in alcohol craving and relapse. We observed, in two animal models of alcohol craving and relapse, that the AMPA antagonist GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] dosedependently reduced cue-induced reinstatement of alcohol-seeking behavior and the alcohol deprivation effect. The involvement of the AMPA receptor in these phenomena was further studied using mice deficient for the GluR-C AMPA subunit [GluR-C knock-out (KO)]. GluR-C KOs displayed a blunted, cue-induced reinstatement response and alcohol deprivation effect, when compared with wild-type controls; however, no differences between genotypes could be observed regarding ethanol self-administration under operant or home cage drinking conditions. These results imply a role for GluR-C in alcohol relapse, although this phenotype could also be attributable to a reduction in the total number of AMPA receptors in specific brain areas. In conclusion, AMPA receptors seem to be involved in the neuroplastic changes underlying alcohol seeking behavior and relapse. Thus, AMPA receptors represent a novel therapeutic target in preventing relapse.

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Section: Discussionmentioning

confidence: 99%

Involvement of the AMPA Receptor GluR-C Subunit in Alcohol-Seeking Behavior and Relapse

Sanchis‐Segura¹,

Borchardt²,

Vengeliene³

et al. 2006

J. Neurosci.

123

112

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“…In contrast, chronic activation of plasticity-related signaling pathways may disrupt memory formation by increasing the noise, therefore reducing instead of enhancing the signal-to-noise ratio (Gerlai et al 1998;Migaud et al 1998;Uetani et al 2000;Pineda et al 2004;Bourtchouladze et al 2006). The situation in VP16-CREB high mice may be similar to that described for flies with the dunce mutation, both VP16-CREB high mice and dunce flies show an enhancement of the cAMP pathway, both show an enhanced response to tetanic stimulation (Kuromi and Kidokoro 2000), and both perform worse than wild-type animals in behavioral tasks (Dudai et al 1976), indicating that from flies to mammals, accurate regulation of the cAMPpathway is required for learning.…”

Section: Discussionmentioning

confidence: 99%

Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

Viosca¹,

Malleret²,

Bourtchouladze³

et al. 2009

Learn. Mem.

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The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene reestablished the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway.

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“…The role of GluA2 in AMPAR trafficking has attracted special attention because it provides a key mechanism for regulating the number of synaptic receptors and plasticity (Malinow and Malenka, 2002;Bredt and Nicoll, 2003;Collingridge et al, 2004;Shepherd and Huganir, 2007;Kerchner and Nicoll, 2008). Thus, genetic disruptions of GluA2 function have been shown to cause dramatic changes in AMPAR functionality and synaptic properties (Jia et al, 1996;Gerlai et al, 1998;Yan et al, 2002;Shimshek et al, 2006a,b;Panicker et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

GluA2 (GluR2) Regulates Metabotropic Glutamate Receptor-Dependent Long-Term Depression through N-Cadherin-Dependent and Cofilin-Mediated Actin Reorganization

Zhou¹,

Hu²,

Passafaro³

et al. 2011

J. Neurosci.

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The GluA2 (GluR2) subunit is critical for the regulation of AMPA receptor properties and synaptic plasticity, but the underlying mechanisms remain unclear. Here, we demonstrate that GluA2 regulates metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) through a previously unknown mechanism involving N-cadherin-dependent and cofilin-mediated actin reorganization. We show that GluA2 is indispensable for mGluR-LTD in the hippocampus, and surprisingly this action of GluA2 is mediated by its extracellular domain interaction with N-cadherin. Accordingly, we show that the function of N-cadherin is regulated by and required for mGluR-LTD. Furthermore, we show that the regulatory effect of GluA2/N-cadherin is mediated through activation of Rho GTPase Rac1 and its downstream actin regulator cofilin, and, importantly, the requirement for GluA2/N-cadherin can be overcome by manipulating cofilin. These results provide compelling evidence that the extracellular domain of GluA2 regulates long-lasting synaptic plasticity through a signaling mechanism that is distinct from those used by the other domains of the receptor subunit.

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Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

Cited by 96 publications

References 52 publications

Involvement of the AMPA Receptor GluR-C Subunit in Alcohol-Seeking Behavior and Relapse

Involvement of the AMPA Receptor GluR-C Subunit in Alcohol-Seeking Behavior and Relapse

Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

GluA2 (GluR2) Regulates Metabotropic Glutamate Receptor-Dependent Long-Term Depression through N-Cadherin-Dependent and Cofilin-Mediated Actin Reorganization

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