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Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits.
J Neurophysiol. 2013 Mar; 109(5):1391-402.JN

Abstract

N-methyl-(D)-aspartate (NMDA) receptors are heteromultimeric ion channels that contain an essential GluN1 subunit and two or more GluN2 (GluN2A-GluN2D) subunits. The biophysical properties and physiological roles of synaptic NMDA receptors are dependent on their subunit composition. In the basolateral amygdala (BLA), it has been suggested that the plasticity that underlies fear learning requires activation of heterodimeric receptors composed of GluN1/GluN2B subunits. In this study, we investigated the subunit composition of NMDA receptors present at synapses on principal neurons in the BLA. Purification of the synaptic fraction showed that both GluN2A and GluN2B subunits are present at synapses, and co-immunoprecipitation revealed the presence of receptors containing both GluN2A and GluN2B subunits. The kinetics of NMDA receptor-mediated synaptic currents and pharmacological blockade indicate that heterodimeric GluN1/GluN2B receptors are unlikely to be present at glutamatergic synapses on BLA principal neurons. Selective RNA interference-mediated knockdown of GluN2A subunits converted synaptic receptors to a GluN1/GluN2B phenotype, whereas knockdown of GluN2B subunits had no effect on the kinetics of the synaptically evoked NMDA current. Blockade of GluN1/GluN2B heterodimers with ifenprodil had no effect, but knockdown of GluN2B disrupted the induction of CaMKII-dependent long-term potentiation at these synapses. These results suggest that, on BLA principal neurons, GluN2B subunits are only present as GluN1/GluN2A/GluN2B heterotrimeric NMDA receptors. The GluN2B subunit has little impact on the kinetics of the receptor, but is essential for the recruitment of signaling molecules essential for synaptic plasticity.

Authors+Show Affiliations

Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23221411

Citation

Delaney, Andrew J., et al. "Synaptic NMDA Receptors in Basolateral Amygdala Principal Neurons Are Triheteromeric Proteins: Physiological Role of GluN2B Subunits." Journal of Neurophysiology, vol. 109, no. 5, 2013, pp. 1391-402.
Delaney AJ, Sedlak PL, Autuori E, et al. Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits. J Neurophysiol. 2013;109(5):1391-402.
Delaney, A. J., Sedlak, P. L., Autuori, E., Power, J. M., & Sah, P. (2013). Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits. Journal of Neurophysiology, 109(5), 1391-402. https://doi.org/10.1152/jn.00176.2012
Delaney AJ, et al. Synaptic NMDA Receptors in Basolateral Amygdala Principal Neurons Are Triheteromeric Proteins: Physiological Role of GluN2B Subunits. J Neurophysiol. 2013;109(5):1391-402. PubMed PMID: 23221411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synaptic NMDA receptors in basolateral amygdala principal neurons are triheteromeric proteins: physiological role of GluN2B subunits. AU - Delaney,Andrew J, AU - Sedlak,Petra L, AU - Autuori,Elenora, AU - Power,John M, AU - Sah,Pankaj, Y1 - 2012/12/05/ PY - 2012/12/11/entrez PY - 2012/12/12/pubmed PY - 2013/8/16/medline SP - 1391 EP - 402 JF - Journal of neurophysiology JO - J Neurophysiol VL - 109 IS - 5 N2 - N-methyl-(D)-aspartate (NMDA) receptors are heteromultimeric ion channels that contain an essential GluN1 subunit and two or more GluN2 (GluN2A-GluN2D) subunits. The biophysical properties and physiological roles of synaptic NMDA receptors are dependent on their subunit composition. In the basolateral amygdala (BLA), it has been suggested that the plasticity that underlies fear learning requires activation of heterodimeric receptors composed of GluN1/GluN2B subunits. In this study, we investigated the subunit composition of NMDA receptors present at synapses on principal neurons in the BLA. Purification of the synaptic fraction showed that both GluN2A and GluN2B subunits are present at synapses, and co-immunoprecipitation revealed the presence of receptors containing both GluN2A and GluN2B subunits. The kinetics of NMDA receptor-mediated synaptic currents and pharmacological blockade indicate that heterodimeric GluN1/GluN2B receptors are unlikely to be present at glutamatergic synapses on BLA principal neurons. Selective RNA interference-mediated knockdown of GluN2A subunits converted synaptic receptors to a GluN1/GluN2B phenotype, whereas knockdown of GluN2B subunits had no effect on the kinetics of the synaptically evoked NMDA current. Blockade of GluN1/GluN2B heterodimers with ifenprodil had no effect, but knockdown of GluN2B disrupted the induction of CaMKII-dependent long-term potentiation at these synapses. These results suggest that, on BLA principal neurons, GluN2B subunits are only present as GluN1/GluN2A/GluN2B heterotrimeric NMDA receptors. The GluN2B subunit has little impact on the kinetics of the receptor, but is essential for the recruitment of signaling molecules essential for synaptic plasticity. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/23221411/Synaptic_NMDA_receptors_in_basolateral_amygdala_principal_neurons_are_triheteromeric_proteins:_physiological_role_of_GluN2B_subunits_ L2 - https://journals.physiology.org/doi/10.1152/jn.00176.2012?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -