Hippocampal-dependent navigation in head-fixed mice using a floating real-world environment

• Published in: Scientific reports Vol. 14; no. 1; pp. 14315 - 13
• Main Authors: Stuart, Sarah A., Palacios-Filardo, Jon, Domanski, Aleks, Udakis, Matt, Duguid, Ian, Jones, Matt W., Mellor, Jack R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/378/1595; 631/378/2591; 631/378/2649; 631/378/87; Animals; Behavior; CA1 Region, Hippocampal - physiology; Computer applications; Environmental effects; Hippocampus; Hippocampus - physiology; Humanities and Social Sciences; Male; Maze Learning; Membrane potential; Membrane Potentials - physiology; Mice; Mice, Inbred C57BL; multidisciplinary; Navigation behavior; Neurosciences; Patch-Clamp Techniques - methods; Pyramidal cells; Pyramidal Cells - physiology; Science; Science (multidisciplinary); Scopolamine; Scopolamine - pharmacology; Spatial Navigation - physiology; Virtual Reality
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-64807-w

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.