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NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear.
Neuropharmacology. 2012 Feb; 62(2):797-806.N

Abstract

Synaptic plasticity mediated by NMDA glutamate receptors is thought to be a primary mechanism underlying the formation of new memories. Activation of GluN2A NMDA receptor subunits may induce long-term potentiation (LTP), whereas low-frequency stimulation of GluN2B receptors induces long-term depression (LTD). In the present study, we show that blockade of GluN2A, but not GluN2B receptors with NVP-AAM077 and Ro25-6981 respectively, prevented LTP of auditory thalamic inputs to the lateral amygdala. Conversely, LTD induction in this pathway was prevented by blockade of GluN2B, but not GluN2A receptors. As this pathway plays a critical role in the acquisition, retrieval and extinction of a learned auditory-cue fear association, we next examined the effects of blockade of GluN2A and GluN2B receptors on the development and retention of a conditioned fear response. Administration of NVP-AAM077, but not Ro25-6981, prior to conditioning disrupted the expression of conditioned fear 24h later. Conversely, Ro25-6981 but not NVP-AAM077 impaired extinction of the conditioned fear response. These data expand on previous work showing that LTP/D in the thalamic-lateral amygdala pathway is dependent on NMDA receptors, by demonstrating selective roles for GluN2A and GluN2B NMDA receptor subunits in LTP and LTD respectively. Furthermore, GluN2A receptor activation and associated LTP may be involved specifically in the initial formation and/or stabilization of a learned fear response, whereas GluN2B receptor activation and associated LTD may facilitate the suppression of Pavlovian fear responses during extinction. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Authors+Show Affiliations

Department of Psychiatry, University of British Columbia, Vancouver, BC V6J 1K8, Canada.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

21925518

Citation

Dalton, Gemma L., et al. "NMDA GluN2A and GluN2B Receptors Play Separate Roles in the Induction of LTP and LTD in the Amygdala and in the Acquisition and Extinction of Conditioned Fear." Neuropharmacology, vol. 62, no. 2, 2012, pp. 797-806.
Dalton GL, Wu DC, Wang YT, et al. NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear. Neuropharmacology. 2012;62(2):797-806.
Dalton, G. L., Wu, D. C., Wang, Y. T., Floresco, S. B., & Phillips, A. G. (2012). NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear. Neuropharmacology, 62(2), 797-806. https://doi.org/10.1016/j.neuropharm.2011.09.001
Dalton GL, et al. NMDA GluN2A and GluN2B Receptors Play Separate Roles in the Induction of LTP and LTD in the Amygdala and in the Acquisition and Extinction of Conditioned Fear. Neuropharmacology. 2012;62(2):797-806. PubMed PMID: 21925518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA GluN2A and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear. AU - Dalton,Gemma L, AU - Wu,Dong Chuan, AU - Wang,Yu Tian, AU - Floresco,Stan B, AU - Phillips,Anthony G, Y1 - 2011/09/10/ PY - 2011/05/26/received PY - 2011/08/29/revised PY - 2011/09/02/accepted PY - 2011/9/20/entrez PY - 2011/9/20/pubmed PY - 2012/7/28/medline SP - 797 EP - 806 JF - Neuropharmacology JO - Neuropharmacology VL - 62 IS - 2 N2 - Synaptic plasticity mediated by NMDA glutamate receptors is thought to be a primary mechanism underlying the formation of new memories. Activation of GluN2A NMDA receptor subunits may induce long-term potentiation (LTP), whereas low-frequency stimulation of GluN2B receptors induces long-term depression (LTD). In the present study, we show that blockade of GluN2A, but not GluN2B receptors with NVP-AAM077 and Ro25-6981 respectively, prevented LTP of auditory thalamic inputs to the lateral amygdala. Conversely, LTD induction in this pathway was prevented by blockade of GluN2B, but not GluN2A receptors. As this pathway plays a critical role in the acquisition, retrieval and extinction of a learned auditory-cue fear association, we next examined the effects of blockade of GluN2A and GluN2B receptors on the development and retention of a conditioned fear response. Administration of NVP-AAM077, but not Ro25-6981, prior to conditioning disrupted the expression of conditioned fear 24h later. Conversely, Ro25-6981 but not NVP-AAM077 impaired extinction of the conditioned fear response. These data expand on previous work showing that LTP/D in the thalamic-lateral amygdala pathway is dependent on NMDA receptors, by demonstrating selective roles for GluN2A and GluN2B NMDA receptor subunits in LTP and LTD respectively. Furthermore, GluN2A receptor activation and associated LTP may be involved specifically in the initial formation and/or stabilization of a learned fear response, whereas GluN2B receptor activation and associated LTD may facilitate the suppression of Pavlovian fear responses during extinction. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/21925518/NMDA_GluN2A_and_GluN2B_receptors_play_separate_roles_in_the_induction_of_LTP_and_LTD_in_the_amygdala_and_in_the_acquisition_and_extinction_of_conditioned_fear_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(11)00395-9 DB - PRIME DP - Unbound Medicine ER -