RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
eNeuro. 2017 May 2;4(3). doi: 10.1523/ENEURO.0369-16.2017. eCollection 2017 May-Jun.
The demonstration of the ability of rodents to navigate in virtual reality (VR) has made it an important behavioral paradigm for studying spatially modulated neuronal activity in these animals. However, their behavior in such simulated environments remains poorly understood. Here, we show that encoding and retrieval of goal location memory in mice head-fixed in VR depends on the postsynaptic scaffolding protein Shank2 and the dorsal hippocampus. In our newly developed virtual cued goal location task, a head-fixed mouse moves from one end of a virtual linear track to seek rewards given at a target location along the track. The mouse needs to visually recognize the target location and stay there for a short period of time to receive the reward. Transient pharmacological blockade of fast glutamatergic synaptic transmission in the dorsal hippocampus dramatically and reversibly impaired performance of this task. Encoding and updating of virtual cued goal location memory was impaired in mice deficient in the postsynaptic scaffolding protein Shank2, a mouse model of autism that exhibits impaired spatial learning in a real environment. These results highlight the crucial roles of the dorsal hippocampus and postsynaptic protein complexes in spatial learning and navigation in VR.
啮齿动物在虚拟现实（VR）中导航的能力已被证明是研究这些动物中空间调节神经元活动的重要行为范式。然而，它们在这种模拟环境中的行为仍未被充分理解。在这里，我们表明，在 VR 中固定头部的小鼠中，目标位置记忆的编码和检索依赖于突触后支架蛋白 Shank2 和背侧海马体。在我们新开发的虚拟提示目标位置任务中，固定头部的小鼠从虚拟线性轨道的一端移动到沿轨道的目标位置获取奖励。小鼠需要通过视觉识别目标位置并在那里停留很短的时间才能获得奖励。背侧海马体中快速谷氨酸能突触传递的短暂药理学阻断显著且可逆地损害了这项任务的表现。在突触后支架蛋白 Shank2 缺失的小鼠（自闭症的小鼠模型，在真实环境中表现出空间学习障碍）中，虚拟提示目标位置记忆的编码和更新受损。这些结果强调了背侧海马体和突触后蛋白复合物在 VR 中的空间学习和导航中的关键作用。
