Sun Wei, Li Xiaoliang, Tang Chunzhi, An Lei
Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
College of Acupuncture-Moxibustion and Orthopedics, Guiyang University of Chinese Medicine, Guiyang, China.
Front Pharmacol. 2018 Dec 6;9:1439. doi: 10.3389/fphar.2018.01439. eCollection 2018.
The hippocampus and striatum guide place-strategy and response-strategy learning, respectively, and they have dissociable roles in memory systems, which could compensate in case of temporary or permanent damage. Although acute alcohol (AA) treatment had been shown to have adverse effects on hippocampal function, whether it causes the functional compensation and the underlying mechanisms is unknown. In this study, rats treated with a low dose of AA avoided a hippocampus-dependent spatial strategy, instead preferring a striatum-dependent response strategy. Consistently, the learning-induced increase in hippocampal, but not striatal, pCREB was rendered less pronounced due to diminished activity of pPKA, but not pERK or pCaMKII. As rats approached the turn-decision area, Sp-cAMP, a PKA activator, was found to mitigate the inhibitory effect of AA on intra- and cross-structure synchronized neuronal oscillations, and rescue response-strategy bias and spatial learning deficits. Our study provides strong evidence of the critical link between neural couplings and strategy selection. Moreover, the PKA/CREB-signaling pathway is involved in the suppressive effect of AA on neural correlates of place-learning strategy. The novel important evidence provided here shows the functional couplings between the hippocampus and striatum in spatial learning processing and suggests possible avenues for therapeutic intervention.
海马体和纹状体分别引导位置策略和反应策略的学习，它们在记忆系统中具有不同的作用，在出现暂时或永久性损伤时可能会起到补偿作用。尽管急性酒精（AA）处理已被证明对海马体功能有不利影响，但其是否会导致功能补偿以及潜在机制尚不清楚。在本研究中，用低剂量AA处理的大鼠避开了依赖海马体的空间策略，转而更喜欢依赖纹状体的反应策略。一致地，由于pPKA活性降低而非pERK或pCaMKII活性降低，学习诱导的海马体而非纹状体中pCREB的增加变得不那么明显。当大鼠接近转弯决策区域时，发现PKA激活剂Sp-cAMP可减轻AA对结构内和跨结构同步神经元振荡的抑制作用，并挽救反应策略偏差和空间学习缺陷。我们的研究提供了神经耦合与策略选择之间关键联系的有力证据。此外，PKA/CREB信号通路参与了AA对位置学习策略神经相关性的抑制作用。此处提供的新的重要证据显示了海马体和纹状体在空间学习过程中的功能耦合，并提出了可能的治疗干预途径。
