Spatial Navigation (Water Maze) Tasks (2008)

Since the early part of the 20th century, a variety of experimental procedures have been developed for animals that employ the escape from water as a means to motivate learning and memory processes [1–4]. Water maze tasks primarily designed to measure spatial learning and recall have become quite useful for evaluating the effects of aging, experimental lesions, and drug effects, especially in rodents. For more than 25 years the Morris water maze (MWM) [5] has been the task most extensively used and accepted by behavioral physiologists and pharmacologists. A cursory literature search revealed that well over 2500 journal articles have been published since 1982 in which this model (or variations of the model) was used to assess and compare spatial learning and memory in rodents.The MWM, while simple at first glance, is a challenging task for rodents that employs a variety of sophisticated mnemonic processes. These processes encompass the acquisition and spatial localization of relevant visual cues that are subsequently processed, consolidated, retained, and then retrieved in order to successfully navigate and thereby locate a hidden platform to escape the water [5] (see also review [6]). The general processes used for “visuospatial navigation” in rats also contribute considerably to human day-to-day cognitive processes. Importantly, several lines of evidence confirm the utility of the model for investigations relevant to the study of neurodegenerative and neuropsychiatric illnesses where cognition is impaired (e.g., Alzheimer’s disease, Parkinson’s disease, schizophrenia). While one would readily acknowledge the differences in complexity between human and rodent behaviors, several salient observations regarding the utility of the MWM are notable: (1) The functional integrity of forebrain cholinergic systems, which are essential for efficient performance of the MWM, appears to be consistently disrupted in patients who suffer from AD. This disruption correlates well with the degree of dementia (see reviews [7,8]) and is also present in many PD patients who suffer cognitive decline [9,10]. (2) Cortical and hippocampal projections from the nucleus basalis magnocellularis (NBM) and medial septum (MS), respectively, are reproducibly devastated in AD (reviewed [7]) and accordingly, reductions in central cholinergic activity in rodents resulting from brain lesions (e.g., NBM, MS, etc.) and age reproducibly impair spatial learning in the MWM (reviewed [6]). (3) Other data implicate the hippocampus as an essential structure for place learning [11], which, incidentally, is commonly atrophic in patients with AD [12,13]. It is interesting to note that the hippocampal formation (in particular the hippocampal-dentate complex and the adjacent entorhinal cortex), which undergoes significant degeneration with age (and particularly so in the setting of dementia), is believed to be intimately involved in cognitive mapping and the facilitation of context-dependent behavior in a changing spatio-temporal setting (reviewed [14]). Evidence to support this premise is now available from living humans where computerized “virtual water maze tasks” have been shown to be highly sensitive to hippocampal dysfunction. For example, in a virtual analogue of the classic MWM hidden platform task (with a three-dimensional pool), patients with unilateral hippocampal resections were severely impaired in their performance relative to age-matched controls and age-matched patients who had extra-hippocampal resections [15]. (4) Anticholinergic agents (e.g., scopolamine), which are routinely used to impair performance in the MWM, also impair memory in humans and worsen the dementia in those with AD [16] (see also review [17]). (5) Finally, it is also important to note that spatial orientation, navigation, learning, and recall (which are used extensively in the MWM) are quite commonly disrupted in patients with dementia. Visuospatial and visuoperceptual deficits and topographic disorientation are detectable very early in the course of AD and become more pronounced as the disease progresses [18–20]. The common observations of spatial and visual agnosia in AD patients also indicate the disruption of complex processes that involve both visual pathways and mnemonic processing [21,22].The MWM procedure offers a number of advantages as a means of assessing cognitive function in rodents when compared to others methods: (1) It requires no pretraining period and can be accomplished in a short period of time with a relatively modest number of animals. For example, young adult, unimpaired (control) rats can accomplish the most commonly employed versions of the task with asymptotic levels of performance achieved in 10–20 trials, generally requiring no more than a few days of testing. (2) Through the use of “training” as well as “probe” or “transfer” trials, learning as well as retrieval processes (spatial bias) [5] can be analyzed and compared between groups. (3) The confounding nature of olfactory trails or cues is eliminated. (4) Through the use of video tracking devices and the measure of swim speeds, non-mnemonic behaviors or strategies (i.e., taxon, praxis, thygmotaxis, etc.) can be delineated and motoric or motivational deficits can be identified. (5) Visible platform tests can identify gross visual deficits that might confound interpretation of results obtained from standard MWM testing. (6) By changing the platform location, both learning and relearning experiments can be accomplished. Accordingly, several doses of experimental drugs can be tested in the same group of animals. (7) While immersion into water may be somewhat unpleasant, more aversive procedures such as food deprivation or exposure to electric shock are circumvented. (8) Through the use of curtains, partitions, etc., operation of the video tracking system by the experimenter out of site of the test subjects also reduces distraction. (9) Finally, the MWM is quite easy to set up in a relatively small laboratory, is comparatively less expensive to operate than many types of behavioral tasks, and is easy to master by research and technical personnel. We have found the method quite useful in drug discovery and development studies for screening compounds for potential cognitive enhancing effects [23], as well as delineating deleterious effects of neurotoxicants on cognition [24]. For a more extensive discussion of the various MWM procedures and their advantages, see Morris [5] and reviews [6,25,26].