Laboratory of Neural Circuits and Plasticity, University of Southern California, 3641 Watt Way, Los Angeles, California; Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany.
Hippocampus. 2013 Dec;23(12):1359-66. doi: 10.1002/hipo.22184. Epub 2013 Sep 10.
Spatial working memory (SWM), the ability to process and manipulate spatial information over a relatively short period of time, requires an intact hippocampus, but also involves other forebrain nuclei in both in rodents and humans. Previous studies in mice showed that the molecular mechanism of SWM includes activation of AMPA receptors containing the GluA1 subunit (encoded by gria1) as GluA1 deletion in the whole brain (gria1(-/-)) results in strong SWM deficit. However, since these mice globally lack GluA1, the circuit mechanisms of GluA1 contribution to SWM remain unknown. In this study, by targeted expression of GluA1 containing AMPA receptors in the forebrain of gria1(-/-) mice or by removing GluA1 selectively from hippocampus of mice with "floxed" GluA1 alleles (gria1(fl/fl) ), we show that SWM requires GluA1 action in cortical circuits but is only partially dependent on GluA1-containing AMPA receptors in hippocampus. We further show that hippocampal GluA1 contribution to SWM is temporally restricted and becomes prominent at longer retention intervals (≥ 30 s). These findings provide a novel insight into the neural circuits required for SWM processing and argue that AMPA mediated signaling across forebrain and hippocampus differentially contribute to encoding of SWM.
空间工作记忆（SWM）是指在相对较短的时间内处理和操纵空间信息的能力，它需要一个完整的海马体，但也涉及到啮齿动物和人类的其他前脑核。以前在小鼠中的研究表明，SWM 的分子机制包括激活含有 GluA1 亚基（由 gria1 编码）的 AMPA 受体，因为大脑中 GluA1 的缺失（gria1(-/-)）导致强烈的 SWM 缺陷。然而，由于这些小鼠在整体上缺乏 GluA1，因此 GluA1 对 SWM 的贡献的回路机制仍不清楚。在这项研究中，通过在 gria1(-/-) 小鼠的前脑或通过从具有“floxed”GluA1 等位基因的小鼠（gria1(fl/fl)）中选择性去除 GluA1 来靶向表达含有 AMPA 受体的 GluA1，我们表明 SWM 需要皮质回路中的 GluA1 作用，但仅部分依赖于海马中的 GluA1 含量 AMPA 受体。我们进一步表明，海马体中的 GluA1 对 SWM 的贡献是时间受限的，并且在较长的保留间隔（≥30s）时变得突出。这些发现为 SWM 处理所需的神经回路提供了新的见解，并表明跨前脑和海马体的 AMPA 介导的信号传递对 SWM 的编码有不同的贡献。
