Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons.

Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons. Research Abstract Details 

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Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons. Abstract Text:

Gary Tong,Hiroto Takahashi,Shichun Tu,Yeonsook Shin,Maria Talantova,Wagner Zago,Peng Xia,Zhiguo Nie,Thomas Goetz,Dongxian Zhang,Stuart A Lipton,Nobuki Nakanishi,Gary Tong,Hiroto Takahashi,Shichun Tu,Yeonsook Shin,Maria Talantova,Wagner Zago,Peng Xia,Zhiguo Nie,Thomas Goetz,Dongxian Zhang,Stuart A Lipton,Nobuki Nakanishi,Gary Tong,Hiroto Takahashi,Shichun Tu,Yeonsook Shin,Maria Talantova,Wagner Zago,Peng Xia,Zhiguo Nie,Thomas Goetz,Dongxian Zhang,Stuart A Lipton,Nobuki Nakanishi,

Expression of the NR3A subunit with NR1/NR2 in Xenopus oocytes or mammalian cell lines leads to a reduction in N-methyl-d-aspartate (NMDA)-induced currents and decreased Mg(2+) sensitivity and Ca(2+) permeability compared with NR1/NR2 receptors. Consistent with these findings, neurons from NR3A knockout (KO) mice exhibit enhanced NMDA-induced currents. Recombinant NR3A can also form excitatory glycine receptors with NR1 in the absence of NR2. However, the effects of NR3A on channel properties in neurons and synaptic transmission have not been fully elucidated. To study physiological roles of NR3A subunits, we generated NR3A transgenic (Tg) mice. Cultured NR3A Tg neurons exhibited two populations of NMDA receptor (NMDAR) channels, reduced Mg(2+) sensitivity, and decreased Ca(2+) permeability in response to NMDA/glycine, but glycine alone did not elicit excitatory currents. In addition, NMDAR-mediated excitatory postsynaptic currents (EPSCs) in NR3A Tg hippocampal slices showed reduced Mg(2+) sensitivity, consistent with the notion that NR3A subunits incorporated into synaptic NMDARs. To study the function of endogenous NR3A subunits, we compared NMDAR-mediated EPSCs in NR3A KO and WT control mice. In NR3A KO mice, the ratio of the amplitudes of the NMDAR-mediated component to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated component of the EPSC was significantly larger than that seen in WT littermates. This result suggests that NR3A subunits contributed to the NMDAR-mediated component of the EPSC in WT mice. Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits.

Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons. Publishing Authors By Initials

G Tong,H Takahashi,S Tu,Y Shin,M Talantova,W Zago,P Xia,Z Nie,T Goetz,D Zhang,SA Lipton,N Nakanishi,G Tong,H Takahashi,S Tu,Y Shin,M Talantova,W Zago,P Xia,Z Nie,T Goetz,D Zhang,SA Lipton,N Nakanishi,G Tong,H Takahashi,S Tu,Y Shin,M Talantova,W Zago,P Xia,Z Nie,T Goetz,D Zhang,SA Lipton,N Nakanishi,

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Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of neurophysiology

VOLUME: 99

Page Numbers: 122-32

Journal Abbreviation: J. Neurophysiol.

ISSN: 0022-3077

DAY: 14

MONTH: 11

YEAR: 2007

Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons. Information

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LANGUAGE: eng

NlmUniqueID: 375404

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AFFILIATION: Burnham Institute for Medical Research, 10901 N. Torrey Pines Rd., La Jolla, CA 92037. gtong@burnham.org).

Country: United States

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MEDLINETA: J Neurophysiol

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