Elsevier

Behavioural Brain Research

Volume 203, Issue 2, 5 November 2009, Pages 151-164
Behavioural Brain Research

Review
Spatial memory: Theoretical basis and comparative review on experimental methods in rodents

https://doi.org/10.1016/j.bbr.2009.05.022Get rights and content

Abstract

The assessment of learning and memory in animal models has been widely employed in scientific research for a long time. Among these models, those representing diseases with primary processes of affected memory – such as amnesia, dementia, brain aging, etc. – studies dealing with the toxic effects of specific drugs, and other exploring neurodevelopment, trauma, epilepsy and neuropsychiatric disorders, are often called on to employ these tools. There is a diversity of experimental methods assessing animal learning and memory skills. Overall, mazes are the devices mostly used today to test memory in rodents; there are several types of them, but their real usefulness, advantages and applications remain to be fully established and depend on the particular variant selected by the experimenter. The aims of the present article are first, to briefly review the accumulated knowledge in regard to spatial memory tasks; second, to bring the reader information on the different types of rodent mazes available to test spatial memory; and third, to elucidate the usefulness and limitations of each of these devices.

Section snippets

Memory

Memory is not a static, isolated or single brain function; memory can be best described as a complex network of different interrelated functions working together to manage information. For this reason, it would be more appropriate to define it in terms of a memory system. Thus, a memory system could be defined as a brain function whose purpose is to classify, encode, store and recover a wide diversity of information relevant for the subject. Interestingly, the taxonomy of these memory systems

Mazes

Mazes are the experimental devices more often employed for global evaluation of spatial memory in rodents, although not the only ones used for this purpose. In general terms, in these devices the animals are food- or water-deprived since food and water are used as behavioural reinforcers. These devices have been employed since the beginning of the past century [133], [137]. The first mazes used for evaluation of animal behaviour were, indeed, reduced adaptations of mazes built in the 17th

Design and general procedure

This device consists of a round pool filled with opaque water. Opacity can be obtained with different substances: powder milk, white paint, titanium dioxide, among others. Inside the pool there is an escape platform slightly hidden (2–3 cm) below the water level (see Fig. 5). The protocol for the study of simple reference spatial memory includes dividing the pool into four equal quadrants (some include two extra concentric-radial divisions). Since water immersion represents an aversive stimulus

Methodological variables

There are multiple methodological variables that need to be considered when using the water maze, and it is now becoming clear how these variables affect the performance of the animals [39]. One variable is the dimensions of the pool, for rats the optimal diameter is between 1.30 and 2 m (according to the original description by Morris). For mice, diameters can oscillate between 75 and 150 cm. Changes in diameter have been found to affect performance in some studies [129], but not in others [128]

Factors influencing animal performance in the Morris water maze

It has been demonstrated that body weight, physical condition and age influence swimming velocity [37]. Several other studies have shown that male animals perform better when compared with females, a fact attributable not only to physical strength but to differences in spatial navigation abilities [16], [111]. One study has shown that these differences disappear when animals are older than 6 months of age, suggesting that the differences reported for younger animals reflect differential

Disadvantages

  • (1)

    Possibly, one of the greatest disadvantages of this device is the use of an aversive behavioural stimulus (aquatic immersion), accounting for the negative effects of stress. It is, however, possible to decrease stress levels by previously exposing the animals to the testing environment (habituation). If, in addition, less sensitive animal strains are employed, the accuracy of the test will be assured. Nevertheless, stress should never be ignored, even if it is assumed that habituation will

Advantages

  • (1)

    Learning is faster in this device than in other mazes (radial maze, circular maze) possibly due to the aversive stimulation. In addition, each trial takes only 60–120 s, and accurate curves of acquisition can be obtained in 5 days of training [53].

  • (2)

    It permits the accurate and reproducible study of reference memory, spatial working memory and learning [37], [39].

  • (3)

    It does not require previous preparation (water or food-deprivation), thus limiting the number of days needed to proceed with

General protocol

It is suggested that each trial last 3 min per animal, with an inter-trial interval of 15 min, with four trials per day during the acquisition phase. The first phase, or habituation, consists of placing the animal on the center of the platform and then, turning on the source of noise or other aversive stimulus. Then the animal is gently taken to the escape hole; once in the escape chamber, all stressful stimuli are turned off, and the animal is kept inside for two additional minutes. Before

Disadvantages

  • (1)

    The most important disadvantage of this device discussed in literature is that learning can be very slow or even absent in some cases, and this has been explained by the lack of stressful stimuli, thereby producing more exploratory behaviour than escape responses as the animals are not sufficiently motivated to escape [116]. In this regard, it has been reported that some animals can reach the entrance of the escape hole, but do not enter, in these cases it is suggested that the latency to reach

Advantages

  • (1)

    The most important advantage of this device is that it does not induce stress, since the aversive stimuli employed here are much less aggressive than those used in other devices [116].

  • (2)

    Similar to the previously described mazes, this one allows the evaluation of learning, working memory and spatial reference memory [116].

  • (3)

    The majority of the studies employing the Barnes maze indicate that it is useful for the study of learning and memory in rats and mice. Particularly, it is suitable for mice

Concluding remarks

Spatial memory evolved in different species possibly because it provides information on spatial locations, objects configuration and specific routes relevant for the preservation and survival of the species. By means of this memory system, animals can locate food sources while preventing risky situations on the basis of previous experiences. Spatial memory recruits different neuronal mechanisms (conscious and unconscious, short- and long-term memory, etc.) to achieve its goal. In this review we

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