Tags

Type your tag names separated by a space and hit enter

Ex vivo depotentiation of conditioning-induced potentiation at thalamic input synapses onto the lateral amygdala requires GluN2B-containing NMDA receptors.
Neurosci Lett. 2012 Nov 21; 530(2):121-6.NL

Abstract

We have previously characterized the ex vivo depotentiation (depotentiation(ex vivo)) of conditioning-induced synaptic potentiation at thalamic input synapses onto the lateral amygdala (T-LA synapses) as a potential cellular substrate for fear extinction: both depotentiation(ex vivo) and fear extinction require NMDA receptors, mitogen-activated protein kinases, metabotropic glutamate receptor 1, de novo protein synthesis and AMPA receptor internalization in the amygdala. Surprisingly, as shown in our and other previous studies, ifenprodil, an antagonist of GluN2B-containing NMDA receptors, fails to inhibit depotentiation(ex vivo) at a saturating concentration (10μM), although it has been suggested that GluN2B-containing NMDA receptors are required for fear extinction. Because ifenprodil is also known to act on other molecular targets in addition to GluN2B-containing NMDA receptors, especially at high concentrations (i.e., ≥10μM), the ineffectiveness of 10μM of ifenprodil may be due to its side effects. Therefore, in the present study, we tested Ro25-6981, a more specific antagonist of GluN2B-containing NMDA receptors, and a lower concentration (3μM) of ifenprodil, which may reduce any possible side effects. Ro25-6981 (3μM) blocked both depotentiation(ex vivo) and late-phase long-term potentiation at T-LA synapses. While 10μM ifenprodil failed to inhibit depotentiation(ex vivo), a lower concentration (3μM) of ifenprodil blocked depotentiation(ex vivo). Together, our findings suggest that depotentiation(ex vivo) requires GluN2B-containing NMDA receptors.

Authors+Show Affiliations

School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, South Korea.No 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

23069667

Citation

Park, Sungmo, et al. "Ex Vivo Depotentiation of Conditioning-induced Potentiation at Thalamic Input Synapses Onto the Lateral Amygdala Requires GluN2B-containing NMDA Receptors." Neuroscience Letters, vol. 530, no. 2, 2012, pp. 121-6.
Park S, Lee S, Kim J, et al. Ex vivo depotentiation of conditioning-induced potentiation at thalamic input synapses onto the lateral amygdala requires GluN2B-containing NMDA receptors. Neurosci Lett. 2012;530(2):121-6.
Park, S., Lee, S., Kim, J., & Choi, S. (2012). Ex vivo depotentiation of conditioning-induced potentiation at thalamic input synapses onto the lateral amygdala requires GluN2B-containing NMDA receptors. Neuroscience Letters, 530(2), 121-6. https://doi.org/10.1016/j.neulet.2012.10.011
Park S, et al. Ex Vivo Depotentiation of Conditioning-induced Potentiation at Thalamic Input Synapses Onto the Lateral Amygdala Requires GluN2B-containing NMDA Receptors. Neurosci Lett. 2012 Nov 21;530(2):121-6. PubMed PMID: 23069667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ex vivo depotentiation of conditioning-induced potentiation at thalamic input synapses onto the lateral amygdala requires GluN2B-containing NMDA receptors. AU - Park,Sungmo, AU - Lee,Sukwon, AU - Kim,Jeongyeon, AU - Choi,Sukwoo, Y1 - 2012/10/13/ PY - 2012/05/26/received PY - 2012/09/25/revised PY - 2012/10/05/accepted PY - 2012/10/17/entrez PY - 2012/10/17/pubmed PY - 2013/5/10/medline SP - 121 EP - 6 JF - Neuroscience letters JO - Neurosci Lett VL - 530 IS - 2 N2 - We have previously characterized the ex vivo depotentiation (depotentiation(ex vivo)) of conditioning-induced synaptic potentiation at thalamic input synapses onto the lateral amygdala (T-LA synapses) as a potential cellular substrate for fear extinction: both depotentiation(ex vivo) and fear extinction require NMDA receptors, mitogen-activated protein kinases, metabotropic glutamate receptor 1, de novo protein synthesis and AMPA receptor internalization in the amygdala. Surprisingly, as shown in our and other previous studies, ifenprodil, an antagonist of GluN2B-containing NMDA receptors, fails to inhibit depotentiation(ex vivo) at a saturating concentration (10μM), although it has been suggested that GluN2B-containing NMDA receptors are required for fear extinction. Because ifenprodil is also known to act on other molecular targets in addition to GluN2B-containing NMDA receptors, especially at high concentrations (i.e., ≥10μM), the ineffectiveness of 10μM of ifenprodil may be due to its side effects. Therefore, in the present study, we tested Ro25-6981, a more specific antagonist of GluN2B-containing NMDA receptors, and a lower concentration (3μM) of ifenprodil, which may reduce any possible side effects. Ro25-6981 (3μM) blocked both depotentiation(ex vivo) and late-phase long-term potentiation at T-LA synapses. While 10μM ifenprodil failed to inhibit depotentiation(ex vivo), a lower concentration (3μM) of ifenprodil blocked depotentiation(ex vivo). Together, our findings suggest that depotentiation(ex vivo) requires GluN2B-containing NMDA receptors. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/23069667/Ex_vivo_depotentiation_of_conditioning_induced_potentiation_at_thalamic_input_synapses_onto_the_lateral_amygdala_requires_GluN2B_containing_NMDA_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(12)01330-4 DB - PRIME DP - Unbound Medicine ER -