Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin

被引:287
作者
Winder, DG [1 ]
Mansuy, IM [1 ]
Osman, M [1 ]
Moallem, TM [1 ]
Kandel, ER [1 ]
机构
[1] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA
关键词
D O I
10.1016/S0092-8674(00)80896-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To investigate the role of phosphatases in synaptic plasticity using genetic approaches, we generated transgenic mice that overexpress a truncated form of calcineurin under the control of the CaMKII alpha promoter. Mice expressing this transgene show increased calcium-dependent phosphatase activity in the hippocampus. Physiological studies of these mice and parallel pharmacological experiments in wild-type mice reveal a novel, intermediate phase of LTP (I-LTP) in the CA1 region of the hippocampus. This intermediate phase differs from E-LTP by requiring multiple trains for induction and in being dependent on PKA. It differs from L-LTP in not requiring new protein synthesis. These data suggest that calcineurin acts as an inhibitory constraint on I-LTP that is relieved by PKA. This inhibitory constraint acts as a gate to regulate the synaptic induction of L-LTP.
引用
收藏
页码:25 / 37
页数:13
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