Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine

Mao, Li; Wang, Wei; Chu, Xiang‐Ping; Zhang, Guo Chi; Liu, Xianyu; Yang, Yuan-Jian; Haines, Michelle; Papasian, Christopher J.; Fibuch, Eugene E.; Buch, Shilpa; Chen, Jian Guo; Wang, John Q.

doi:10.1038/nn.2300

Cited by 106 publications

(107 citation statements)

References 48 publications

(71 reference statements)

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“…However, it is clear that additional insights can be gained by furthering these studies to include the dynamics of protein expression and degradation (7,8). In the brain, for example, protein turnover is critical to synaptic plasticity (32,33). Here, we report a large-scale analysis of in vivo protein turnover in mice, a commonly used model organism for the study of mammalian biology.…”

Section: Discussionmentioning

confidence: 98%

“…This work provides the methodology and theoretical framework necessary to conduct proteome-wide analyses of in vivo protein turnover in any model organism and environmental condition where a labeled diet can be incorporated into the experimental design. The approach will be generally useful in analyzing relationships between proteome homeostasis and biological phenotypes of interest, particularly in the brain, where protein turnover is critical to normal function (32,33) and accumulation of misfolded protein aggregates is a primary characteristic of neurodegenerative disease (44,45).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

335

447

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Fig. 2. (A)Interaction web of top-down and bottom-up effects in the eelgrass study system. The top predator is the sea otter (E. lutris), the mesopredators are crabs (Cancer spp. and Pugettia producta), the epiphyte mesograzers are primarily an isopod (I. resecata) and a sea slug (P. taylori), and algal epiphyte competitors of eelgrass primarily consist of chain-forming diatoms, and the red alga Smithora naiadum. Solid arrows indicate direct effects, dashed arrows indicate indirect effects, and the plus and minus symbols indicate positive and/or negative effects on trophic guilds and eelgrass condition. C, competitive interaction; T, trophic interaction. (Original artwork by A. C. Hughes.) (B-E) Survey results testing for the effects of sea otter density on eelgrass bed community properties (Tables S2 and S3). Elkhorn Slough (sea otters present and high nutrients) eelgrass beds (n = 4) are coded in red, and the Tomales Bay reference site (no sea otters, low nutrients) beds (n = 4) are coded in blue. (B) Crab biomass and size structure of two species of Cancer crabs; (C) grazer biomass per shoot and large grazer density; (D) algal epiphyte loading; and (E) aboveground and belowground eelgrass biomass. DW, dry weight; FW, fresh weight.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

335

447

View full text Add to dashboard Cite

show abstract

“…The extinction-reinstatement model, which best recapitulates the abstinence-relapse paradigm seen in human addicts (Schmidt et al, 2005;Epstein et al, 2006;Knackstedt and Kalivas, 2009), could determine if lack of Kal7 affects sensitivity to stress, drug, or contextinduced reinstatement. Additionally, studies examining NR2B inhibition in cocaine self-administration in Wt and Kal7 KO animals will be important to understanding the significance of the direct interaction of Kal7 and NR2B , the failure of self-administered cocaine to increase NAc NR2B expression in Kal7 KO mice, and the critical role of NR2B in the behavioral response to cocaine (Ma et al, 2006;Huang et al, 2009;Mao et al, 2009;Brown et al, 2011;Kiraly et al, 2011;Pascoli et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Constitutive Knockout of Kalirin-7 Leads to Increased Rates of Cocaine Self-Administration

et al. 2013

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Kalirin-7 (Kal7) is a Rho-guanine nucleotide exchange factor that is localized in neuronal postsynaptic densities. Kal7 interacts with the NR2B subunit of the NMDA receptor and regulates aspects of dendritic spine dynamics both in vitro and in vivo. Chronic treatment with cocaine increases dendritic spine density in the nucleus accumbens (NAc) of rodents and primates. Kal7 mRNA and protein are upregulated in the NAc following cocaine treatment, and the presence of Kal7 is necessary for the normal proliferation of dendritic spines following cocaine use. Mice that constitutively lack Kal7 [Kalirin-7 knockout mice (Kal7 KO )] demonstrate increased locomotor sensitization to cocaine and a decreased place preference for cocaine. Here, using an intravenous cocaine self-administration paradigm, Kal7 KO mice exhibit increased administration of cocaine at lower doses as compared with wildtype (Wt) mice. Analyses of mRNA transcript levels from the NAc of mice that self-administered saline or cocaine reveal that larger splice variants of the Kalrn gene are increased by cocaine more dramatically in Kal7 KO mice than in Wt mice. Additionally, transcripts encoding the NR2B subunit of the NMDA receptor increased in Wt mice that self-administered cocaine but were unchanged in similarly experienced Kal7 KO mice. These findings suggest that Kal7 participates in the reinforcing effects of cocaine, and that Kal7 and cocaine interact to alter the expression of genes related to critical glutamatergic signaling pathways in the NAc.

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“…5), previously shown to lead to the disappearance of withdrawal anxiety (Van Sickle et al, 2004). Thus the depression of NMDAR function during FZP withdrawal may act as a compensatory negative feedback mechanism to protect the neuron from AMPAR-mediated overactivation as in amygdala neurons during fear conditioning (Zinebi et al, 2001(Zinebi et al, , 2003, striatal neurons after chronic amphetamine exposure (Mao et al, 2009), or spinal cord nociceptive synapses during chronic peripheral inflammation (Vikman et al, 2008). The reduction of GluN2B subunit-mediated NMDAR currents would serve as a homeostatic mechanism to offset neuronal hyperactivity generated by the progressive enhancement of AMPAR current and thus may serve as a physiological brake to down-regulate neuronal output, limiting withdrawal symptoms such as anxiety.…”

Section: Regulation Of Nmdar During Benzodiazepine Withdrawal 271mentioning

confidence: 98%

Down-Regulation of Synaptic GluN2B Subunit-Containing N-methyl-d-aspartate Receptors: A Physiological Brake on CA1 Neuron α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Hyperexcitability during Benzodiazepine Withdrawal

Shen

Tietz²

2010

J Pharmacol Exp Ther

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A significant link was previously established between benzodiazepine withdrawal anxiety and a progressive increase in ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) potentiation in hippocampal CA1 neurons from rats withdrawn up to 2 days from 1-week oral administration of the benzodiazepine flurazepam (FZP). Despite AMPAR current potentiation, withdrawal anxiety was masked by a 2-fold reduction in CA1 neuron N-methyl-D-aspartate receptor (NMDAR) currents since preinjection of an NMDA antagonist restored NMDAR currents and unmasked anxiety in 2-day FZP-withdrawn rats. In the current study, GluN subunit levels in postsynaptic density (PSD)-enriched subfractions of CA1 minislices were compared with GluN2B-mediated whole-cell currents evoked in CA1 neurons in hippocampal slices from 1-and 2-day FZP-withdrawn rats. GluN1 and GluN2B, although not the phosphoSer1303-GluN2B ratio or GluN2A subunit levels, were decreased in PSD subfractions from 2-day, but not 1-day, FZP-withdrawn rats. Consistent with immunoblot analyses, GluN2B-mediated NMDAR currents evoked in slices from 2-day FZP-withdrawn rats were decreased in the absence, but not the presence, of the GluN2B subunit-selective antagonist ifenprodil. In contrast, ifenprodil-sensitive NMDAR currents were unchanged in slices from 1-day withdrawn rats. Because AMPA (1 M) preincubation of slices from 1-day FZP-withdrawn rats induced depression of GluN2B subunit-mediated currents, depression of NMDAR currents was probably secondary to AMPAR potentiation. CA1 neuron NMDAR currents were depressed ϳ50% after 2-day withdrawal and offset potentiation of AMPAR-mediated currents, leaving total charge transfer unchanged between groups. Collectively, these findings suggest that a reduction of GluN2B-containing NMDAR may serve as a homeostatic feedback mechanism to modulate glutamatergic synaptic strength during FZP withdrawal to alleviate benzodiazepine withdrawal symptoms.

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Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine

Cited by 106 publications

References 48 publications

Analysis of proteome dynamics in the mouse brain

Analysis of proteome dynamics in the mouse brain

Constitutive Knockout of Kalirin-7 Leads to Increased Rates of Cocaine Self-Administration

Down-Regulation of Synaptic GluN2B Subunit-Containing N-methyl-d-aspartate Receptors: A Physiological Brake on CA1 Neuron α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Hyperexcitability during Benzodiazepine Withdrawal

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