Directional responding of C57BL/6J mice in the Morris water maze is influenced by visual and vestibular cues and is dependent on the anterior thalamic nuclei.

Recent findings indicate that rats navigate in spatial tasks such as the Morris water maze (MWM) using a local cue-based reference frame rather than a distal cue-based reference frame. Specifically, rats swim in a particular direction to a location relative to pool-based cues, rather than to an absolute location defined by room-based cues. Neural mechanisms supporting this bias in rodents for relative responding in spatial tasks are not yet understood. Anterior thalamic neurons discharge according to the current directional heading of the animal. The contribution of head direction (HD) cell activity to navigation has been difficult to elucidate. We found that male C57BL/6J mice trained for 4 or 7 d in the MWM exhibited an overwhelming preference for swimming in a direction relative to pool-based cues over absolute responding during a platform-less probe test. Rotation of extramaze cues caused a corresponding rotation of the direction mice swam during the probe test, suggesting that both pool- and room-based reference frames guide platform search. However, disorienting the mice before the probe test disturbed relative responding. Therefore, relative responding is guided by both internal and external cue sources. Selective inactivation of anterior thalamic nuclei (ATN) by microinfusion of muscimol or fluorophore-conjugated muscimol caused a near complete shift in preference from relative to absolute responding. Interestingly, inactivation of the dorsal CA1 region of the hippocampus did not affect relative responding. These data suggest that ATN, and HD cells therein, may guide relative responding in the MWM, a task considered by most to reflect hippocampal processing.