Experimental Flexibility and Adaptability of the MWM

The variation in visible and hidden platforms make the MWM highly adaptable. Specific, working memory versions of the maze are available (Morris 1984;Stewart and Morris 1993) [14][15] .

. Use of dual targets and variation in start location allows for discrimination between hippocampal and striatal learning; rats with striatal lesions cannot learn the task, while those with lesions in the hippocampus can.

Inserting structures into the pool helps poorly performing, inbred strains of mice learn faster; however, structures have little benefit for normal performers and may impact results.

Due to variations in apparatus and testing procedures, researchers are advised to review Morris’ work: foundations (Morris 1981)[16] and methods (Morris 1984; Stewart and Morris 1993)[17][18] in conjunction with methodological improvements (Vorhees and Williams 2006; Wenk 2004)[19][20].

Pool and Platform Size

Pool size was virtually doubled by Morris during his original research. Since then, little systematic study of this variable has been discovered. Faster learning is seen in smaller pools, but if the pool is too small, the task is too easy (Mactutus and Booze 1994)[21].

Pools that are too large could also impact results, but successful learning assessments have been recorded in pools of up to 244-cm (Williams et al. 2014)[22] – a larger boundary has not yet been established. A small pool is typically used for adult mice, which may be beneficial; there is evidence that mice cannot learn in a 210-cm pool (Schaefer et al. 2011)[23]. In a comparison between 122-cm and 152-cm diameter pools where wild-type C57BL/6J mice were used, the mice in the smaller pool found the platform faster on day 1, but on days 2 to 5 and beyond, both groups showed similar rates of improvement.

Search Area to Target Ratio

Target size also impacts task difficulty, and relative ratio of ‘pool-to-target’ allows systematic study relative to task difficulty. A 10cm platform in a 122-cm tank creates a ratio of 149:1 – conditions in which many mouse strains learn well (a 210-cm pool with a 10cm platform shows almost no learning in mice) (Schaefer et al. 2011)[24]. Pool-to-platform ratio can be used to determine task difficulty, but some ratios do not seem to be adequately navigable by mice, unless they are subject to an acceptable ratio first and it is gradually altered.

Rats, on the other hand, learn well even in the higher ratios (larger pools and smaller platforms). Neonatal exposure to methamphetamine has a dramatic difference on performance when compared to controls (Williams et al. 2003b, 2004)[25][26]. Lowering the platform size in stages, however, produced good learning curves in both the methamphetamine exposed and control rats (Vorhees et al. 2008)[27], demonstrating pool-to-platform ratio as moderated by prior experience.

Cues, Platforms and Starting Location

Learning proficiency is drastically changed using distal cues. Rats have a minimal threshold of required cues in allocentric navigation: a minimum of two separate distal cues, in addition to the pool edge (Maurer and Derivaz 2000)[28]. A study in which the starting location moves demonstrates rats with hippocampal lesions use relative position for navigation (Morris et al. 1990, Hamilton et al. 2007)[29][30] and use distal and directional cues together.

Cued exposure before hidden trials reduces problems associated with learning subordinate task skills, such as staying on the platform or searching away from the wall. This has significant value in mice trials, as they are prone to behaviors that reduce learning (thigmotaxis, floating or not recognizing the platform). Trials with cues have positive skill transfer with a modest flattening of the learning curve in just a single day’s exposure, and 6 trials.

Dividing the pool into four cardinal zones creates different start locations for the typical four trials per day. The variation in start locations creates a saw-tooth pattern due to platform proximity, but learning curves must be smooth in order to eliminate distance variance (Morris 1981; Vorhees et al. 1995, Vorhees and Williams 2006)[31][32][33].

Phases and Trial Type

Adding a reversal phase (moving the platform to an opposing quadrant) highlights unseen deficits in simple acquisition phases. Reversal deficits are seen in subjects with hippocampal lesions or receptors blockades, as the animals are unable to ‘give up’ – behaviour otherwise learned through multiple attempts to locate the acquisition platform (Whishaw and Tomie 1997)[34]. This could be the result of spatial learning problems, or interference effects from inflexibility rather than cognitive remapping. If pre-training or cued trails are used before testing, NMDA inhibition is prevalent, eliminating acquisition, but not reversal deficits (Hoh et al. 1999)[35].

Probe trials, a.k.a.”memory trials,” remove the platform where subjects spend their time searching. If the location has been learned previously, the animal will have a preference for the platform’s quadrant. Assessing reference versus working memory relies on sufficient time between trials, otherwise animals use short-term memory instead of consolidated memory. In order to accurately measure reference memory, 24 hours must pass after platform trials (Baldi et al. 2005)[36].