%0 Journal Article
%T Hippocampal-dependent navigation in head-fixed mice using a floating real-world environment.
%A Stuart SA
%A Palacios-Filardo J
%A Domanski A
%A Udakis M
%A Duguid I
%A Jones MW
%A Mellor JR
%J Sci Rep
%V 14
%N 1
%D 2024 06 21
%M 38906952
%F 4.996
%R 10.1038/s41598-024-64807-w
%X 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.