Pi4KIIα Regulates Unconditioned Stimulus-Retrieval-Induced Fear Memory Reconsolidation through Endosomal Trafficking of AMPA Receptors

被引：15

作者：

Guo, Hongling ^{[1
]}

Yuan, Kai ^{[1
]}

Zhang, Zhongyu ^{[2
,3
]}

Xue, Yanxue ^{[2
,3
]}

Yan, Wei ^{[1
]}

Meng, Shiqiu ^{[2
,3
]}

Zhu, Weili ^{[2
,3
]}

Wu, Ping ^{[2
,3
]}

Bao, Yanping ^{[2
,3
]}

Shi, Jie ^{[2
,3
]}

Zhang, Wen ^{[2
,3
]}

Lu, Lin ^{[1
,4
,5
]}

Han, Ying ^{[2
,3
]}

机构：

[1] Peking Univ, Natl Clin Res Ctr Mental Disorders, Hosp 6, Inst Mental Hlth,NHC Key Lab Mental Hlth, 51 Huayuan Bei Rd, Beijing 100191, Peoples R China

[2] Peking Univ, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 100191, Peoples R China

[3] Peking Univ, Beijing Key Lab Drug Dependence, 38 Xueyuan Rd, Beijing 100191, Peoples R China

[4] Peking Univ, McGovern Inst Brain Res, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[5] Peking Univ, McGovern Inst Brain Res, PKU IDG, Beijing 100871, Peoples R China

来源：

ISCIENCE | 2020年 / 23卷 / 03期

基金：

中国国家自然科学基金;

关键词：

PHOSPHATIDYLINOSITOL; 4-KINASE; MOLECULAR-MECHANISMS; DENDRITIC SPINES; II-ALPHA; AMYGDALA; PROPRANOLOL; PROTEINS; ONSET;

D O I：

10.1016/j.isci.2020.100895

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Targeting memory reconsolidation is an effective intervention for treating posttraumatic stress disorder (PTSD). Disrupting unconditioned stimulus (US)-retrieval-induced fear memory reconsolidation has become an effective therapeutic approach to attenuate fear memory, but the underlying molecular mechanisms remain unknown. Here, we report that US-retrieval-dependent increase in phosphatidylinositol 4-kinase II alpha (Pi4KII alpha) promotes early endosomal trafficking of AMPA receptors, leading to the enhancement of synaptic efficacy in basolateral amygdala (BLA) neurons. The inhibition of Pi4KII alpha by an inhibitor or short hairpin RNA impaired contextual fear memory reconsolidation. This disruptive effect persisted for at least 2 weeks, which was restored by Pi4KII alpha overexpression with TAT-Pi4KII alpha. Furthermore, the blockade of early endosomal trafficking following US retrieval reduced synaptosomal membrane GluA1 levels and decreased subsequent fear expression. These data demonstrate that Pi4KII alpha in the BLA is crucial for US-retrieval-induced fear memory reconsolidation, the inhibition of which might be an effective therapeutic strategy for treating PTSD.

引用

页数：31