Go Mary Ann, Rogers Jake, Gava Giuseppe P, Davey Catherine E, Prado Seigfred, Liu Yu, Schultz Simon R
Department of Bioengineering and Centre for Neurotechnology, Imperial College London, London, United Kingdom.
Department of Biomedical Engineering, University of Melbourne, Melbourne, VIC, Australia.
Front Cell Neurosci. 2021 Feb 12;15:618658. doi: 10.3389/fncel.2021.618658. eCollection 2021.
The hippocampal place cell system in rodents has provided a major paradigm for the scientific investigation of memory function and dysfunction. Place cells have been observed in area CA1 of the hippocampus of both freely moving animals, and of head-fixed animals navigating in virtual reality environments. However, spatial coding in virtual reality preparations has been observed to be impaired. Here we show that the use of a real-world environment system for head-fixed mice, consisting of an air-floating track with proximal cues, provides some advantages over virtual reality systems for the study of spatial memory. We imaged the hippocampus of head-fixed mice injected with the genetically encoded calcium indicator GCaMP6s while they navigated circularly constrained or open environments on the floating platform. We observed consistent place tuning in a substantial fraction of cells despite the absence of distal visual cues. Place fields remapped when animals entered a different environment. When animals re-entered the same environment, place fields typically remapped over a time period of multiple days, faster than in freely moving preparations, but comparable with virtual reality. Spatial information rates were within the range observed in freely moving mice. Manifold analysis indicated that spatial information could be extracted from a low-dimensional subspace of the neural population dynamics. This is the first demonstration of place cells in head-fixed mice navigating on an air-lifted real-world platform, validating its use for the study of brain circuits involved in memory and affected by neurodegenerative disorders.
啮齿动物的海马体位置细胞系统为记忆功能及功能障碍的科学研究提供了一个主要范例。在自由活动动物以及在虚拟现实环境中导航的头部固定动物的海马体CA1区域均观察到了位置细胞。然而，已观察到虚拟现实实验中的空间编码受损。在此，我们表明，对于头部固定的小鼠，使用由带有近端线索的气浮轨道组成的真实世界环境系统，在空间记忆研究方面比虚拟现实系统具有一些优势。我们对注射了基因编码钙指示剂GCaMP6s的头部固定小鼠的海马体进行成像，这些小鼠在浮动平台上的圆形受限或开放环境中导航。尽管没有远端视觉线索，我们在相当一部分细胞中观察到了一致的位置调谐。当动物进入不同环境时，位置野会重新映射。当动物重新进入同一环境时，位置野通常会在数天的时间段内重新映射，比自由活动实验中的速度更快，但与虚拟现实实验相当。空间信息率在自由活动小鼠观察到的范围内。流形分析表明，空间信息可以从神经群体动力学的低维子空间中提取。这是首次在头部固定的小鼠在气浮真实世界平台上导航时证明位置细胞的存在，验证了其在研究参与记忆且受神经退行性疾病影响的脑回路方面的用途。
