Li, BM (reprint author), Fudan Univ, Inst Neurobiol, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China,firstname.lastname@example.org
It is known that N-methyl-D-aspartate (NMDA) receptor in the basolateral nucleus of amygdala (BLA) is essential for fear memory formation. NMDA NR2B and NR2A subtype receptors exhibit difference in electrophysiological and signaling properties. However, it is unclear whether these two subtype receptors have different roles in fear memory formation. Here, we provide evidence, using pharmacological blockade and genetic interference, that NR2B is involved in acquisition of auditory fear memory in a conditioning-strength dependent way. Pre-conditioning intra-BLA infusion of the NR2B selective antagonist ifenprodil or Ro25-6981 impaired 48-h auditory fear memory (AFM) induced by five but not one CS-US pairing protocol, while similar treatment with the NR2A antagonist NVP-AAM077 disrupted memory for both protocols. Consistently, genetic over-expression of NR2B C-terminal in the BLA, which interferes with the C-terminal mediated intracellular signaling, produced a severe deficit in 48-h AFM for five but not one CS-US pairing protocol, whereas over-expression of NR2A C-terminal impaired memory for both protocols. Furthermore, pre-conditioning infusion of ifenprodil down-regulated the elevated phosphorylation level of extracellular signal-regulated kinase (ERK) induced by five CS-US pairing protocol. Thus, the involvement of BLA NR2B in AFM acquisition depends on conditioning strength. (C) 2008 Published by Elsevier Ltd.
Zhang, Xue-Han; Liu, Fang; Chen, Qian; Zhang, Chun-Lei; Zhuo, Min; Xiong, Zhi-Qi; Li, Bao-Ming.Conditioning-strength dependent involvement of NMDA NR2B subtype receptor in the basolateral nucleus of amygdala in acquisition of auditory fear memory,NEUROPHARMACOLOGY,2008,55(2):238-246