Hippocampal long-term depression is required for the consolidation of spatial memory

被引：224

作者：

Ge, Yuan ^{[1
,2
]}

Dong, Zhifang ^{[1
,3
,4
]}

Bagot, Rosemary C. ^{[5
,6
]}

Howland, John G. ^{[1
]}

Phillips, Anthony G. ^{[1
]}

Wong, Tak Pan ^{[1
,5
,6
]}

Wang, Yu Tian ^{[1
,2
]}

机构：

[1] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada

[2] China Med Univ Hosp, Translat Med Res Ctr, Ctr Neuropsychiat, Grad Inst Immunol, Taichung 40447, Taiwan

[3] Chongqing Med Univ, Minist Educ, Chongqing 400014, Peoples R China

[4] Chongqing Med Univ, Childrens Hosp, City Joint Key Lab Child Dev & Disorders, Paediat Inst, Chongqing 400014, Peoples R China

[5] Douglas Mental Hlth Univ Inst, Montreal, PQ H4H 1R3, Canada

[6] McGill Univ, Montreal, PQ H4H 1R3, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 38期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

hippocampus; learning and memory; long-term potentiation; AMPA receptor endocytosis; Morris water maze; BIDIRECTIONAL SYNAPTIC PLASTICITY; NR2B-CONTAINING NMDA RECEPTORS; RAT HIPPOCAMPUS; IN-VIVO; NOVELTY ACQUISITION; DEPENDENT LTD; NR2B SUBUNIT; POTENTIATION; MICE; CA1;

D O I：

10.1073/pnas.1008200107

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：

Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are candidate mechanisms for long-term spatial memory, the precise contributions of LTP and LTD remain poorly understood. Here, we report that LTP and LTD in the hippocampal CA1 region of freely moving adult rats were prevented by NMDAR 2A (GluN2A) and 2B subunit (GluN2B) preferential antagonists, respectively. These results strongly suggest that NMDAR subtype preferential antagonists are appropriate tools to probe the roles of LTP and LTD in spatial memory. Using a Morris water maze task, the LTP-blocking GluN2A antagonist had no significant effect on any aspect of performance, whereas the LTD-blocking GluN2B antagonist impaired spatial memory consolidation. Moreover, similar spatial memory deficits were induced by inhibiting the expression of LTD with intrahippocampal infusion of a short peptide that specifically interferes with AMPA receptor endocytosis. Taken together, our findings support a functional requirement of hippocampal CA1 LTD in the consolidation of long-term spatial memory.

引用

页码：16697 / 16702

页数：6

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