Nie Ting, McDonough Conor B, Huang Ted, Nguyen Peter V, Abel Ted
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Neurosci. 2007 Sep 19;27(38):10278-88. doi: 10.1523/JNEUROSCI.1602-07.2007.
Studies of hippocampal long-term potentiation (LTP), a cellular model of memory storage, implicate cAMP-dependent protein kinase (PKA) in presynaptic and postsynaptic mechanisms of LTP. The anchoring of PKA to AKAPs (A kinase-anchoring proteins) creates compartmentalized pools of PKA, but the roles of presynaptically and postsynaptically anchored forms of PKA in late-phase LTP are unclear. In this study, we have created genetically modified mice that conditionally express Ht31, an inhibitor of PKA anchoring, to probe the roles of anchored PKA in hippocampal LTP and spatial memory. Our findings show that at hippocampal Schaffer collateral CA3-CA1 synapses, theta-burst LTP requires presynaptically anchored PKA. In addition, a pool of anchored PKA in hippocampal area CA3 is required for spatial memory. These findings reveal a novel and significant role for anchored PKA signaling in cellular mechanisms underlying memory storage.
海马体长期增强效应(LTP)是一种记忆存储的细胞模型,相关研究表明,环磷酸腺苷(cAMP)依赖性蛋白激酶(PKA)参与了LTP的突触前和突触后机制。PKA与A激酶锚定蛋白(AKAPs)结合,形成了PKA的分隔池,但PKA在突触前和突触后锚定形式在晚期LTP中的作用尚不清楚。在本研究中,我们构建了条件性表达PKA锚定抑制剂Ht31的转基因小鼠,以探究锚定PKA在海马体LTP和空间记忆中的作用。我们的研究结果表明,在海马体的沙费尔侧支CA3-CA1突触中,θ波爆发式LTP需要突触前锚定的PKA。此外,海马体CA3区的一组锚定PKA对空间记忆是必需的。这些发现揭示了锚定PKA信号在记忆存储的细胞机制中具有新的重要作用。