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

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• Head-fixation in mice allows detailed neuronal monitoring but often limits sensory engagement.
• Virtual reality offers visual simulation, but a mobile homecage (MHC) could provide a richer, multi-sensory environment.
• The suitability of MHC for behavioral tasks and its impact on neuronal representations were previously unknown.

Purpose of the Study:

• To assess if mice behave similarly in an MHC as in real environments.
• To determine if MHC can support validated maze-based behavioral tasks.
• To investigate hippocampal function and neuronal dynamics during navigation in the MHC.

Main Methods:

• Utilized a mobile homecage (MHC) system for head-fixed mice.
• Performed whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons.
• Trained mice in an adapted T-maze with spatial cues and reversed contingencies, assessing learning with and without scopolamine infusions.

Main Results:

• Hippocampal place cell representations remained intact within the MHC.
• The MHC system facilitated long-duration (20 min) recordings of sub-threshold membrane potential dynamics.
• Mice successfully learned and relearned reward locations in the T-maze, demonstrating hippocampus-dependent, cholinergic-dependent navigation.

Conclusions:

• The mobile homecage (MHC) is a viable experimental platform for studying complex behaviors in head-fixed mice.
• MHC supports intact hippocampal function, including place cell activity and spatial learning.
• This system enables the investigation of sub-threshold membrane potential dynamics underlying navigation.