Hullinger Rikki, O'Riordan Kenneth, Burger Corinna
Neuroscience Training Program, University of Wisconsin-Madison, USA.
Department of Pharmacology & Therapeutics, Biotechnology (Watts) Building, Trinity College, Dublin 2, Ireland(1).
Neurobiol Learn Mem. 2015 Nov;125:126-34. doi: 10.1016/j.nlm.2015.08.006. Epub 2015 Sep 2.
Previous studies from our lab have demonstrated that mild cognitive impairments identified early in life are predictive of cognitive deficits that develop with age, suggesting that enhancements in cognition at an early age can provide a buffer against age-related cognitive decline. Environmental enrichment has been shown to improve learning and memory in the rodent, but the impact of enrichment on synaptic plasticity and the molecular mechanisms behind enrichment are not completely understood. To address these unresolved issues, we have housed 2-month old rats in environmentally enriched (EE), socially enriched (SE), or standard housing (SC) and conducted tests of learning and memory formation at various time intervals. Here we demonstrate that animals that have been exposed to one month of social or environmental enrichment demonstrate enhanced learning and memory relative to standard housed controls. However, we have found that after 4months EE animals perform better than both SE and SC groups and demonstrate an enhanced hippocampal LTP. Our results demonstrate that this LTP is dependent on mGluR5 signaling, activation of ERK and mTOR signaling cascades, and sustained phosphorylation of p70s6 kinase, thus providing a potential target mechanism for future studies of cognitive enhancement in the rodent.
我们实验室之前的研究表明,生命早期识别出的轻度认知障碍可预测随年龄增长而出现的认知缺陷,这表明早年认知能力的增强可以缓冲与年龄相关的认知衰退。环境丰富化已被证明可改善啮齿动物的学习和记忆,但丰富化对突触可塑性的影响以及丰富化背后的分子机制尚未完全了解。为了解决这些未解决的问题,我们将2个月大的大鼠饲养在环境丰富(EE)、社交丰富(SE)或标准饲养(SC)环境中,并在不同时间间隔进行学习和记忆形成测试。在这里,我们证明,与标准饲养的对照组相比,接受一个月社交或环境丰富化的动物表现出增强的学习和记忆能力。然而,我们发现,4个月后,EE组动物的表现优于SE组和SC组,并表现出增强的海马长时程增强(LTP)。我们的结果表明,这种LTP依赖于代谢型谷氨酸受体5(mGluR5)信号传导、细胞外信号调节激酶(ERK)和雷帕霉素靶蛋白(mTOR)信号级联的激活,以及p70核糖体蛋白S6激酶(p70s6激酶)的持续磷酸化,从而为未来啮齿动物认知增强研究提供了潜在的靶标机制。