Enhanced learning and memory in GAT1 heterozygous mice  

作　　者：Jun Shi Youqing Cai Guoxiang Liu Neng Gong Zhenze Liu Tianle Xu Zhugang Wang Jian Fei 

机构地区：[1]Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China [2]Institute of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China [3]School of Life Science and Technology,Tongji University,Shanghai200092,China [4]Shanghai Research Center for Model Organistns,Shanghai 201210,China

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第4期359-366,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by grants from the National Key Basic Research Program founded by MOST （2010CB945501, 2010CB912604）, the Science and Technology Commission of Shanghai Municipality （10140901400, 10410703800）, and the National Natural Science Foundation of China （81171300）.

摘　　要：γ-Aminobutyric acid （GABA） is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters （GAT1-4）. It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1^-/- mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1^＋/- mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behav- ior in such mice. As one form of synaptic plasticity, long- term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1^＋/- mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1^-/- mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice.γ-Aminobutyric acid （GABA） is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters （GAT1-4）. It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1^-/- mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1^＋/- mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behav- ior in such mice. As one form of synaptic plasticity, long- term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1^＋/- mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1^-/- mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice.

关 键 词：GAT1 COGNITION LTP HIPPOCAMPUS MICROARRAY 

分 类 号：Q492.4[生物学—生理学] S813.23[农业科学—畜牧学]