Ex vivo depotentiation of conditioning-induced potentiation at thalamic input synapses onto the lateral amygdala requires GluN2B-containing NMDA receptors.
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.
School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-742, South Korea.
Sungmo
S
Park
Sukwon
S
Lee
Jeongyeon
J
Kim
Sukwoo
S
Choi
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate