Mesh : Animals Mice Spatial Navigation / physiology Maze Learning Male Hippocampus / physiology Pyramidal Cells / physiology Mice, Inbred C57BL Membrane Potentials / physiology CA1 Region, Hippocampal / physiology Virtual Reality Scopolamine / pharmacology Patch-Clamp Techniques / methods

来  源:   DOI:10.1038/s41598-024-64807-w   PDF(Pubmed)

Abstract:
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
摘要:
小鼠的头部固定能够实现对神经元活动的高分辨率监测以及对环境刺激的精确控制。虚拟现实可用于模拟头部固定过程中运动的视觉体验,而是一个低惯性的浮动现实世界环境(移动家园,MHC)有可能参与更多的感官模式,并为复杂的行为任务提供更丰富的实验环境。然而,不知道老鼠是否以与真实环境相似的方式对这种适应环境做出反应,或者MHC是否可以用来实施验证,基于迷宫的行为任务。这里,我们显示海马位置细胞表示在MHC中是完整的,并且该系统允许从背侧CA1锥体神经元进行相对较长(20分钟)的全细胞膜片钳记录,揭示亚阈值膜电位动力学。此外,小鼠在二维空间导航线索的引导下,在适应的T迷宫中学习液体奖励的位置,并在空间偶然性反转时重新学习位置。双侧注射东pol碱表明,这种学习是海马依赖性的,需要完整的胆碱能信号。因此,我们将MHC系统描述为研究支持复杂导航行为的亚阈值膜电位动力学的实验工具。
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