Freudenberg Florian, Resnik Evgeny, Kolleker Alexander, Celikel Tansu, Sprengel Rolf, Seeburg Peter H
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main, Germany; Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Neurobiol Learn Mem. 2016 Nov;135:83-90. doi: 10.1016/j.nlm.2016.07.005. Epub 2016 Jul 11.
Spatial working memory (SWM) is an essential cognitive function important for survival in a competitive environment. In rodents SWM requires an intact hippocampus and SWM expression is impaired in mice lacking the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 (Gria1 mice). Here we used viral gene transfer to show that re-expression of GluA1 in the hippocampus can affect the behavioral performance of GluA1 deficient mice. We found that Gria1 mice with hippocampus-specific rescue of GluA1 expression (Gria1 mice) are more anxious, less hyperactive and only partly impaired in SWM expression in the Y-maze spatial novelty preference paradigm compared to Gria1 mice. However, Gria1 mice still express SWM performance deficits when tested in the rewarded alternation T-maze task. Thus, the restoration of hippocampal function affects several behaviors of GluA1 deficient mice - including SWM expression - in different tasks. The virus-mediated GluA1 expression in Gria1 mice is not sufficient for a comprehensive SWM restoration, suggesting that both hippocampal as well as extra-hippocampal GluA1-containing AMPA receptors contribute to SWM.
空间工作记忆（SWM）是一种重要的认知功能，对在竞争环境中生存至关重要。在啮齿动物中，SWM需要完整的海马体，并且在缺乏α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluA1的小鼠（Gria1小鼠）中，SWM表达受损。在这里，我们使用病毒基因转移来表明海马体中GluA1的重新表达可以影响GluA1缺陷小鼠的行为表现。我们发现，与Gria1小鼠相比，在海马体中特异性拯救GluA1表达的Gria1小鼠（Gria1小鼠）更焦虑，活动亢进程度更低，并且在Y迷宫空间新奇偏好范式中的SWM表达仅部分受损。然而，当在奖励交替T迷宫任务中进行测试时，Gria1小鼠仍然表现出SWM性能缺陷。因此，海马体功能的恢复会影响GluA1缺陷小鼠的多种行为——包括SWM表达——在不同任务中。病毒介导的Gria1小鼠中GluA1的表达不足以实现全面的SWM恢复，这表明海马体以及海马体外含GluA1的AMPA受体都对SWM有贡献。
