Characterization and Comparison of the NR3A Subunit of the NMDA Receptor in Recombinant Systems and Primary Cortical Neurons

Sasaki, Y.; Rothe, Thomás; Premkumar, Louis S.; Das, Saumya; Cui, Jiankun; Talantova, Maria; Wong, Hon Kit; Gong, Xiaowen; Chan, Shing Fai; Zhang, Dongxian; Nakanishi, Norihiko; Sucher, Nikolaus J.; Lipton, Stuart A.

doi:10.1152/jn.00531.2001

Cited by 171 publications

(194 citation statements)

References 34 publications

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“…In addition to NR1 and NR2, the NMDA channel conductance would also be influenced by the presence of an NR3 subunit (Das et al, 1998). However, the conductance levels of NR3-containing heteromeres are very different from those recorded here (Green and Gibb, 2001;Sasaki et al, 2002). Moreover, expression of NR3 protein in mouse cortical neurons peaks during the first week of life and then falls steadily, such that none is present by P20 (Sasaki et al, 2002) when the vast majority of our channel recordings were made.…”

Section: Discussionmentioning

confidence: 88%

NMDA Receptors in Layer 4 Spiny Stellate Cells of the Mouse Barrel Cortex Contain the NR2C Subunit

Binshtok

Fleidervish²,

Sprengel

et al. 2006

J. Neurosci.

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In layer 4 of the somatosensory cortex, the glutamatergic synapses that interconnect spiny stellate (SpS) neurons, which are the major targets of thalamocortical input, differ from most other neocortical excitatory synapses in that they have an extremely large NMDA receptor (NMDAR)-mediated component that is relatively insensitive to voltage-dependent Mg 2ϩ blockade. We now report that this unique feature of the NMDA response reflects the distinctive subunit composition of the underlying receptors. We studied NMDARmediated miniature EPSCs (mEPSCs) and NMDA channel currents in tangential brain slices of mouse barrel cortex, which exclusively contain layer 4. NMDAR-mediated mEPSCs in SpS neurons were prominent at negative membrane potentials, and NMDA channels in outside-out patches excised from the somata of the same neurons had relatively low conductance and reduced susceptibility to Mg 2ϩ block. These are characteristic features of heteromeric NMDAR assemblies that contain the NR2C subunit. Some patches also contained NMDA channels with higher conductance and a greater sensitivity to Mg 2ϩ . In the neocortex of transgenic mice in which a ␤-galactosidase (lacZ) indicator gene was controlled by the NR2C promoter, the lacZ indicator was densely expressed in layer 4. In current-clamp recordings, blockade of NMDARs caused hyperpolarization and an increase in apparent input resistance. Our data demonstrate that the SpS neurons of layer 4 functionally express NR2C subunits; this is the likely explanation for their ability to generate large NMDAR-mediated EPSPs that are effective at resting potential, without previous depolarization.

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Section: Discussionmentioning

confidence: 88%

NMDA Receptors in Layer 4 Spiny Stellate Cells of the Mouse Barrel Cortex Contain the NR2C Subunit

Binshtok

Fleidervish²,

Sprengel

et al. 2006

J. Neurosci.

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“…These findings are especially important given the lack of antibodies, specific pharmacological tools and electrophysiological properties that distinguish NR2C-containing receptors. Although lower sensitivity to magnesium block and low channel conductance are frequently used to identify NMDARs as NR2C-containing, these are not properties uniquely conferred by the NR2C subunit Sasaki et al, 2002). Therefore, knowing the precise patterns of NR2 and NR3 subunit expression is of major importance when considering if an NMDA channel is NR2C-containing, as recently reported for layer IV spiny stellate cells of the mouse barrel cortex (Binshtok et al, 2006).…”

Section: Neuronal Expression Of Nr2c In Non-cerebellar Neuronsmentioning

confidence: 99%

Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-β-galactosidase knock-in mice

Karavanova

Vasudevan

Cheng

et al. 2007

Molecular and Cellular Neuroscience

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NMDA receptor "knock-in" mice were generated by inserting the nuclear β-galactosidase reporter at the NR2C subunit translation initiation site. Novel cell-types and dynamic patterns of NR2C expression were identified using these mice, which were unnoticed before because reagents that specifically recognize NR2C-containing receptors are non-existent. We identified a transition zone from NR2C-expressing neurons to astrocytes in an area connecting the retrosplenial cortex and hippocampus. We demonstrate that NR2C is expressed in a subset of S100β-positve/GFAP-negative glial cells in the striatum, olfactory bulb and cerebral cortex. We also demonstrate novel areas of neuronal expression such as retrosplenial cortex, thalamus, pontine and vestibular nuclei. In addition, we show that during cerebellar development NR2C is expressed in transient caudalrostral gradients and parasagittal bands in subsets of granule cells residing in the internal granular layer, further demonstrating heterogeneity of granule neurons. These results point to novel functions of NR2C-containing NMDA receptors.

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“…Thus, tonic and STCs were produced by a release of glutamate or of another endogenous agonist of the glutamate binding site. The lack of effect of D-serine also excludes the involvement of NMDA receptors containing NMDAR3 subunits, because these receptors, unlike other NMDA receptors, are blocked by Dserine (Chatterton et al, 2002;Sasaki et al, 2002).…”

Section: Slow Transient and Tonic Nmda Currents In Hippocampal Pyramimentioning

confidence: 99%

Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus

Angulo¹,

Kozlov²,

Charpak³

et al. 2004

J. Neurosci.

459

473

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Glial cells of the nervous system directly influence neuronal and synaptic activities by releasing transmitters. However, the physiological consequences of this glial transmitter release on brain information processing remain poorly understood. We demonstrate here in hippocampal slices of 2-to 5-week-old rats that glutamate released from glial cells generates slow transient currents (STCs) mediated by the activation of NMDA receptors in pyramidal cells. STCs persist in the absence of neuronal and synaptic activity, indicating a nonsynaptic origin of the source of glutamate. Indeed, STCs occur spontaneously but can also be induced by pharmacological tools known to activate astrocytes and by the selective mechanical stimulation of single nearby glial cells. Bath application of the inhibitor of the glutamate uptake DL-threo-␤-benzyloxyaspartate increases both the frequency of STCs and the amplitude of a tonic conductance mediated by NMDA receptors and probably also originated from glial glutamate release. By using dual recordings, we observed synchronized STCs in pyramidal cells having their soma distant by Ͻ100 m. The degree of precision (Ͻ100 msec) of this synchronization rules out the involvement of calcium waves spreading through the glial network. It also indicates that single glial cells release glutamate onto adjacent neuronal processes, thereby controlling simultaneously the excitability of several neighboring pyramidal cells. In conclusion, our results show that the glial glutamate release occurs spontaneously and synchronizes the neuronal activity in the hippocampus.

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Characterization and Comparison of the NR3A Subunit of the NMDA Receptor in Recombinant Systems and Primary Cortical Neurons

Cited by 171 publications

References 34 publications

NMDA Receptors in Layer 4 Spiny Stellate Cells of the Mouse Barrel Cortex Contain the NR2C Subunit

NMDA Receptors in Layer 4 Spiny Stellate Cells of the Mouse Barrel Cortex Contain the NR2C Subunit

Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-β-galactosidase knock-in mice

Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus

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