Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, South Korea; Department of Pharmacology, Wonkwang University School of Medicine, Iksan 54538, South Korea.
School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, South Korea.
Brain Res Bull. 2018 Jul;141:50-57. doi: 10.1016/j.brainresbull.2018.04.011. Epub 2018 Apr 20.
Memory reconsolidation is the process by which previously consolidated memories reenter a labile state through reactivation of the memory trace and are actively consolidated through de novo protein synthesis. Although extensive studies have shown that β-adrenergic signaling plays a critical role in the restabilization of reactivated memory, its role in the destabilization of long-term memory is not well-studied. In this study, we found that membrane excitability increased in hippocampal CA1 neurons immediately after the retrieval of contextual fear memory. Interestingly, this increase in membrane excitability diminished after treatment with propranolol (a β-adrenergic receptor antagonist), an NMDA receptor antagonist, and a PKA inhibitor. In addition, we found that administration of propranolol prior to, but not after, the retrieval of fear memory ameliorated the memory impairment caused by anisomycin, indicating that inhibition of β-adrenergic signaling blocks the destabilization of contextual fear memory. Taken together, these results indicate that β-adrenergic signaling via NMDA receptors and PKA signaling pathway induces a labile state of long-term memory through increased neuronal membrane excitability.
记忆再巩固是指先前巩固的记忆通过记忆痕迹的重新激活重新进入不稳定状态，并通过新的蛋白质合成而被主动巩固的过程。尽管大量研究表明β-肾上腺素能信号在重新激活记忆的再稳定中起着关键作用，但它在长时记忆的不稳定中的作用尚未得到很好的研究。在这项研究中，我们发现，在提取情境恐惧记忆后，海马 CA1 神经元的膜兴奋性立即增加。有趣的是，这种膜兴奋性的增加在普萘洛尔（β-肾上腺素能受体拮抗剂）、NMDA 受体拮抗剂和 PKA 抑制剂处理后减弱。此外，我们发现，在恐惧记忆提取之前而不是之后给予普萘洛尔，可以改善放线菌酮引起的记忆障碍，表明抑制β-肾上腺素能信号会阻止情境恐惧记忆的不稳定。总之，这些结果表明，通过 NMDA 受体和 PKA 信号通路的β-肾上腺素能信号通过增加神经元膜兴奋性诱导长时记忆的不稳定状态。
