Enhanced learning and memory in GAT1 heterozygous 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 behavior 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.
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jun
J
Shi
Youqing
Y
Cai
Guoxiang
G
Liu
Neng
N
Gong
Zhenze
Z
Liu
Tianle
T
Xu
Zhugang
Z
Wang
Jian
J
Fei
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006579:Heterozygote; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D009435:Synaptic Transmission / Q000502:physiology
D050485:GABA Plasma Membrane Transport Proteins