Assessing Spatial Learning and Memory in Rodents

Abstract

Maneuvering safely through the environment is central to survival of almost all species. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and nearby proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures; in humans this system encodes allocentric, semantic, and episodic memory. This form of memory is assessed in laboratory animals in many ways, but the dominant form of assessment is the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and, when overlearned, becomes procedural memory. In this article, several allocentric assessment methods for rodents are reviewed and compared with the MWM. MWM advantages (little training required, no food deprivation, ease of testing, rapid and reliable learning, insensitivity to differences in body weight and appetite, absence of nonperformers, control methods for proximal cue learning, and performance effects) and disadvantages (concern about stress, perhaps not as sensitive for working memory) are discussed. Evidence-based design improvements and testing methods are reviewed for both rats and mice. Experimental factors that apply generally to spatial navigation and to MWM specifically are considered. It is concluded that, on balance, the MWM has more advantages than disadvantages and compares favorably with other allocentric navigation tasks.

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

“…Regarding the differences between male and female rats, the female rats had enhanced exploratory activity, but no differences in cognitive functions were observed. In most tests of allocentric navigation in rodents, male animals show an advantage compared with female animals, while in some egocentric navigation tasks, female rats performed better than male rats (Vorhees & Williams, 2014), or no sex differences were observed; thus, the sex differences depend on the specific task parameters and/or configurations Roof & Stein, 2001;Vorhees & Williams, 2014;Sutcliffe, Marshall, & Neill, 2007;Locklear & Kritzer, 2014). The new substrain of rats developed in our laboratory showed decreased exploratory activity and learning ability in the AMBITUS system, which is in agreement with the results obtained recently in novel object recognition and the hole-board tests (Petrovszki et al, 2013;Kekesi et al, 2015), and it suggests that this system can be applied to reveal the abnormalities in these parameters of rats with different impairments.…”

“…Different mazes and hole-boards with food rewards are commonly used in this regard. Rats show spontaneous exploratory activity in new environment, which may correspond to a form of information acquisition (Vorhees & Williams, 2014). Searching for food is also a naturally motivated behavior; thus, rodents are able to learn to retrieve food rewards located in different setups (Post et al, 2011;Vorhees & Williams, 2014).…”

“…Rats show spontaneous exploratory activity in new environment, which may correspond to a form of information acquisition (Vorhees & Williams, 2014). Searching for food is also a naturally motivated behavior; thus, rodents are able to learn to retrieve food rewards located in different setups (Post et al, 2011;Vorhees & Williams, 2014). Some researchers have used a circular corridor with a few (3) side boxes (only in the outer side) with food rewards to investigate the learning capability of rodents (Wikenheiser et al, 2013;Wikenheiser & Redish, 2015;Wikenheiser & Redish, 2011).…”

“…Evaluation of chemically-induced neurotoxicity in laboratory rodents or animal models of several diseases associated with learning and memory decline (e.g., depression, Parkinson disease, senile dementia or brain trauma, schizophrenia, and autism) are frequently expected to test locomotor activity, learning, and memory functions (Fitzgerald, Rosenberg, Oettinger, & Battig, 1985;Vorhees & Williams, 2014;Brown et al, 2012;Chrobal, Hanin, & Walsh, 1987;Hauser, Sontag, Tucha, & Lange, 2012;Preissmann, Bertholet, Sierro, Cabungcal, & Schenk, 2011).…”

“…Several methods are available to determine the learning ability of rodents during relatively short time period and/or repeated short trials, including novel object recognition, hole-board, and several mazes, e.g., Y maze, T maze, Morris Water maze, Barnes maze, or radial mazes with different number of arms (Casarrubea, Sorbera, Magnusson, & Crescimanno, 2010;Xu et al, 2013;Chambon, Wegener, Gravius, & Danysz, 2011;Petrovszki et al, 2013;Fitzgerald et al, 1985;Chrobal et al, 1987;Gordan et al, 2012;Locklear & Kritzer, 2014;McLean, Woolley, & Neill, 2009;van der Staay, Gieling, Pinzón, Nordquist, & Ohl, 2012;Vorhees & Williams, 2014;Roof & Stein, 2001;Vorhees & Williams, 2014). Other, more sophisticated methods, such as tasks with touch screen or lever press, require very intensive and long-lasting learning sessions (Brown et al, 2012;Chen, Wong, Chapman, & Pemberton, 2009;de Bruin et al, 2013;Dunnett, Fuller, Rosser, & Brooks, 2012;Nemeth et al, 2002;Preissmann et al, 2011;Sabbagh, Heaney, Bolton, Murtishaw, & Kinney, 2012;Bussey et al, 2008;George, RodriguezSantiago, Riley, & Abelson, 2015).…”