Background

The Barnes maze is a dry-land based behavioral test that was originally developed by Carol Barnes to study spatial memory in rats (Barnes, 1979) and later adapted for use in mice (Bach et al., 1995). Conceptually, it is similar to the Morris water maze (MWM) (Morris, 1984), in that it is a hippocampal-dependent task where animals learn the relationship between distal cues in the surrounding environment and a fixed escape location. For mice, the typical Barnes maze setup consists of an elevated circular platform with 40 evenly-spaced holes around the perimeter. An escape tunnel is mounted underneath one hole while the remaining 39 holes are left empty. Both bright light and open spaces are aversive to rodents, thus serve as motivating factors to induce escape behavior. The escape tunnel is maintained at a fixed location for the duration of training, which involves multiple daily trials spread over several days. During the course of training, rodents typically utilize a sequence of three different search strategies (random, serial, spatial) to learn the location of the escape tunnel. Following sufficient acquisition training, the escape tunnel is removed and a probe trial is administered to assess spatial reference memory.

Although the MWM is the dominant model for assessing spatial learning in rodents, the Barnes maze offers several important advantages worth noting. First and foremost, the Barnes maze does not involve swimming and the potential confounding factors associated with it. Swimming is stressful, as detailed in studies documenting that MWM training increases plasma corticosterone levels to a greater extent than that of the Barnes maze (Harrison et al., 2009). In addition, the swim conditions utilized in most MWM protocols elicit reductions in core body temperature that can affect performance (Iivonen et al., 2003). Moreover, rodents often take to floating, which is thought to represent a state of behavioral despair and is considered an index of ‘depressive-like’ behavior in the widely utilized Porsolt forced swim test (Porsolt et al., 1977). Finally, as noted above, the Barnes maze allows clear delineation of the three possible search strategies used by the mouse during performance of each trial.