钙调神经磷酸酶抑制的一种新型长期增强中间阶段的遗传和药理学证据。

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

作者信息

Winder D G, Mansuy I M, Osman M, Moallem T M, Kandel E R

机构信息

Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York 10032, USA.

出版信息

Cell. 1998 Jan 9;92(1):25-37. doi: 10.1016/s0092-8674(00)80896-x.

DOI:10.1016/s0092-8674(00)80896-x

PMID:9489697

Abstract

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 CaMKIIalpha 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.

摘要

为了利用遗传学方法研究磷酸酶在突触可塑性中的作用，我们构建了在CaMKIIα启动子控制下过表达截短形式钙调神经磷酸酶的转基因小鼠。表达该转基因的小鼠海马体中钙依赖性磷酸酶活性增加。对这些小鼠的生理学研究以及在野生型小鼠中进行的平行药理学实验揭示了海马体CA1区一种新的中间阶段长时程增强（I-LTP）。这个中间阶段与早期长时程增强（E-LTP）不同，诱导I-LTP需要多串刺激且依赖蛋白激酶A（PKA）。它与晚期长时程增强（L-LTP）不同，不需要新的蛋白质合成。这些数据表明钙调神经磷酸酶对I-LTP起抑制性限制作用，PKA可解除这种限制。这种抑制性限制起到一个闸门的作用，调节L-LTP的突触诱导。