Development and Validation of a Novel Framework to Study the Neural Basis of Spatial Learning and Navigation in Rodents

Abstract

The ability of an organism to navigate towards remembered locations requires an internal representation of space. This representation can be referenced against either external cues (landmark-based navigation) or internal vestibular and proprioceptive cues (path integration). While it has been shown that the hippocampus is essential for spatial cognition, the precise neurobiological underpinnings of our ability to navigate to locations stored in spatial memory is not well understood. Recent electrophysiological and behavioural evidence suggests hilar mossy cells may play a functionally significant role in spatial cognition. However, spatial mazes previously described in the literature are confounded by stress or otherwise incompatible with capturing mossy cell involvement in spatial learning. Here I developed the Hidden Food Maze (HFM), in which mice learn to find a food reward in a large circular arena that requires no experimenter handling. I show that the HFM produces reliable learning curves in C57Bl/6 mice and that a robust learning criterion can be established. Notably, I found that mice rely predominantly on path integration when only distal visual cues are available in the HFM task. Preliminary results suggest that intra-maze cues are available, mice use them for their initial orientation and then appear to use path integration after cue identification. For my Master’s Thesis, I will describe results from only experiments with distal visual cues. I conclude that the Hidden Food Maze provides a naturalistic assessment of spatial learning in mice, in a format that is amenable for in vivo electrophysiological and imaging approaches from awake and behaving animals and thus provides a powerful and flexible means to investigate the neural bases of navigation.