Conditioning-strength dependent involvement of NMDA NR2B subtype receptor in the basolateral nucleus of amygdala in acquisition of auditory fear memory.
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.
Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Xue-Han
XH
Zhang
Fang
F
Liu
Qian
Q
Chen
Chun-Lei
CL
Zhang
Min
M
Zhuo
Zhi-Qi
ZQ
Xiong
Bao-Ming
BM
Li
D000161:Acoustic Stimulation / Q000009:adverse effects; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005239:Fear; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005818:Genetic Engineering; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011601:Psychophysics; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D010446:Peptide Fragments; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione; C121001:NR2B NMDA receptor; C485184:enhanced green fluorescent protein