Locomotory patterns, spatiotemporal organization of exploration and spatial memory in serotonin transporter knockout mice

Serotonin transporter knockout (SERT−/−) mice are extensively used as a genetic model of several neuropsychiatric disorders, and consistently display anxiety-like behaviors and inactivity in different tests. To better understand how these mice organize their behavior, we assessed the open field and elevated plus maze spatiotemporal patterning of activity in adult male SERT wild type (+/+), heterozygous (+/−) and −/− mice on C57BL/6J genetic background using new videotracking and analytic procedures. In addition, we analyzed their spatial memory, assessing within- and between-trial habituation, and examined specific motor characteristics of their movement in these two tests. In the open field test, SERT−/− mice showed reduced vertical exploration throughout the arena, reduced central (but not peripheral) horizontal exploration, unaltered within-trial habituation, and slightly poorer between-trial habituation for horizontal activity. In the elevated plus maze, SERT−/− mice demonstrated anxiety-like avoidance of open arms, hypoactivity, as well as unaltered within-trial and between-trial habituation (except for poorer between-trial habituation of total horizontal activity). In both tests, SERT−/− mice showed greater prevalence of horizontal over vertical dimension of their exploration in the areas protected by the walls (open field periphery, plus maze closed arms), but not in open aversive areas, such as the center of the open field or center or open arms of the maze. In both arenas, SERT−/− mice consistently displayed increased turning behavior, potentially representing a perseverance-like phenotype or aberrant spatial strategies in novel environments. Overall, using a fine-graded behavioral analysis in two different novelty tests, this study revealed alterations in motor and spatiotemporal patterning of activity in SERT−/− mice. Given the relevance of exploratory strategies to human personality traits and brain disorders, our data may be useful for developing further neurobehavioral models using these mice.