scholarly journals Regulation of dendritic spine growth through activity-dependent recruitment of the brain-enriched Na+/H+ exchanger NHE5

2011 ◽  
Vol 22 (13) ◽  
pp. 2246-2257 ◽  
Author(s):  
Graham H. Diering ◽  
Fergil Mills ◽  
Shernaz X. Bamji ◽  
Masayuki Numata
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Receptor Activation ◽  
Neuronal Activation ◽  
Activity Dependent ◽  
The Brain ◽  
Nmda Receptor Activation

Subtle changes in cellular and extracellular pH within the physiological range have profound impacts on synaptic activities. However, the molecular mechanisms underlying local pH regulation at synapses and their influence on synaptic structures have not been elucidated. Dendritic spines undergo dynamic structural changes in response to neuronal activation, which contributes to induction and long-term maintenance of synaptic plasticity. Although previous studies have indicated the importance of cytoskeletal rearrangement, vesicular trafficking, cell signaling, and adhesion in this process, much less is known about the involvement of ion transporters. In this study we demonstrate that N-methyl-d-aspartate (NMDA) receptor activation causes recruitment of the brain-enriched Na+/H+ exchanger NHE5 from endosomes to the plasma membrane. Concomitantly, real-time imaging of green fluorescent protein–tagged NHE5 revealed that NMDA receptor activation triggers redistribution of NHE5 to the spine head. We further show that neuronal activation causes alkalinization of dendritic spines following the initial acidification, and suppression of NHE5 significantly retards the activity-induced alkalinization. Perturbation of NHE5 function induces spontaneous spine growth, which is reversed by inhibition of NMDA receptors. In contrast, overexpression of NHE5 inhibits spine growth in response to neuronal activity. We propose that NHE5 constrains activity-dependent dendritic spine growth via a novel, pH-based negative-feedback mechanism.

scholarly journals NMDA Reduces Tau Phosphorylation in Rat Hippocampal Slices by Targeting NR2A Receptors, GSK3β, and PKC Activities

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Audrée De Montigny ◽  
Ismaël Elhiri ◽  
Julie Allyson ◽  
Michel Cyr ◽  
Guy Massicotte
Keyword(s):  
Nmda Receptor ◽  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
Hippocampal Slices ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Receptor Activation ◽  
Tau Phosphorylation ◽  
Cell Death Mechanisms ◽  
Nmda Receptor Activation

The molecular mechanisms that regulate Tau phosphorylation are complex and currently incompletely understood. In the present study, pharmacological inhibitors were deployed to investigate potential processes by which the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors modulates Tau phosphorylation in rat hippocampal slices. Our results demonstrated that Tau phosphorylation at Ser199-202 residues was decreased in NMDA-treated hippocampal slices, an effect that was not reproduced at Ser262 and Ser404 epitopes. NMDA-induced reduction of Tau phosphorylation at Ser199-202 was further promoted when NR2A-containing receptors were pharmacologically isolated and were completely abrogated by the NR2A receptor antagonist NVP-AAM077. Compared with nontreated slices, we observed that NMDA receptor activation was reflected in high Ser9 and low Tyr216 phosphorylation of glycogen synthase kinase-3 beta (GSK3β), suggesting that NMDA receptor activation might diminish Tau phosphorylation via a pathway involving GSK3βinhibition. Accordingly, we found that GSK3βinactivation by a protein kinase C- (PKC-) dependent mechanism is involved in the NMDA-induced reduction of Tau phosphorylation at Ser199-202 epitopes. Taken together, these data indicate that NR2A receptor activation may be important in limiting Tau phosphorylation by a PKC/GSK3βpathway and strengthen the idea that these receptors might act as an important molecular device counteracting neuronal cell death mechanisms in various pathological conditions.

scholarly journals Rapid regulation of endoplasmic reticulum dynamics in dendritic spines by NMDA receptor activation

2014 ◽  
Vol 7 (1) ◽  
Author(s):  
Ai Na Ng ◽  
Andrew J Doherty ◽  
Paul J Lombroso ◽  
Nigel J Emptage ◽  
Graham L Collingridge
Keyword(s):  
Endoplasmic Reticulum ◽  
Nmda Receptor ◽  
Dendritic Spines ◽  
Receptor Activation ◽  
Nmda Receptor Activation

scholarly journals Paradoxical signaling regulates structural plasticity in dendritic spines

2016 ◽  
Vol 113 (36) ◽  
pp. E5298-E5307 ◽  
Author(s):  
Padmini Rangamani ◽  
Michael G. Levy ◽  
Shahid Khan ◽  
George Oster
Keyword(s):  
Dendritic Spines ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Structural Plasticity ◽  
Receptor Activation ◽  
Protein Activity ◽  
Actin Remodeling ◽  
Dependent Protein ◽  
Nmda Receptor Activation

Transient spine enlargement (3- to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.

scholarly journals Paradoxical signaling regulates structural plasticity in dendritic spines

2016 ◽  
Author(s):  
Padmini Rangamani ◽  
Michael G. Levy ◽  
Shahid M. Khan ◽  
George Oster
Keyword(s):  
Differential Equation ◽  
Dendritic Spines ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Structural Plasticity ◽  
Receptor Activation ◽  
Protein Activity ◽  
Nmda Receptor Activation ◽  
Spine Dynamics

AbstractTransient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine en­largement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling net­works and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remod­eling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.

scholarly journals Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation

2002 ◽  
Vol 99 (3) ◽  
pp. 1661-1664 ◽  
Author(s):  
L. Scott ◽  
M. S. Kruse ◽  
H. Forssberg ◽  
H. Brismar ◽  
P. Greengard ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Receptor Activation ◽  
D1 Receptors ◽  
Dopamine D1 Receptors ◽  
Nmda Receptor Activation

scholarly journals NMDA Receptor Activation and Calpain Contribute to Disruption of Dendritic Spines by the Stress Neuropeptide CRH

2013 ◽  
Vol 33 (43) ◽  
pp. 16945-16960 ◽  
Author(s):  
Adrienne L. Andres ◽  
Limor Regev ◽  
Lucas Phi ◽  
Ronald R. Seese ◽  
Yuncai Chen ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Receptor Activation ◽  
Nmda Receptor Activation
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