钙刺激的腺苷酸环化酶活性对于海马体依赖的长期记忆和晚期长时程增强至关重要。

Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP.

作者信息

Wong S T, Athos J, Figueroa X A, Pineda V V, Schaefer M L, Chavkin C C, Muglia L J, Storm D R

机构信息

Department of Pharmacology, University of Washington School of Medicine, Seattle 98195, USA.

出版信息

Neuron. 1999 Aug;23(4):787-98. doi: 10.1016/s0896-6273(01)80036-2.

DOI:10.1016/s0896-6273(01)80036-2

PMID:10482244

Abstract

It is hypothesized that Ca2+ stimulation of calmodulin (CaM)-activated adenylyl cyclases (AC1 or AC8) generates cAMP signals critical for late phase LTP (L-LTP) and long-term memory (LTM). However, mice lacking either AC1 or AC8 exhibit normal L-LTP and LTM. Here, we report that mice lacking both enzymes (DKO) do not exhibit L-LTP or LTM. To determine if these defects are due to a loss of cAMP increases in the hippocampus, DKO mice were unilaterally cannulated to deliver forskolin. Administration of forskolin to area CA1 before training restored normal LTM. We conclude that Ca2+-stimulated adenylyl cyclase activity is essential for L-LTP and LTM and that AC1 or AC8 can produce the necessary cAMP signal.

摘要

据推测，钙（Ca2+）对钙调蛋白（CaM）激活的腺苷酸环化酶（AC1或AC8）的刺激会产生对晚期长时程增强（L-LTP）和长期记忆（LTM）至关重要的环磷酸腺苷（cAMP）信号。然而，缺乏AC1或AC8的小鼠表现出正常的L-LTP和LTM。在此，我们报告，缺乏这两种酶的小鼠（双敲除小鼠，DKO）不表现出L-LTP或LTM。为了确定这些缺陷是否是由于海马体中cAMP增加的缺失所致，对DKO小鼠进行单侧插管以给予福斯高林。在训练前向CA1区给予福斯高林可恢复正常的LTM。我们得出结论，钙刺激的腺苷酸环化酶活性对L-LTP和LTM至关重要，并且AC1或AC8可以产生必要的cAMP信号。