Working Memory Y-Maze Test for Xenopus Tadpoles

Working memory refers to the multifaceted cognitive systems that are considered necessary for retaining information while performing complex tasks, such as reasoning and learning in humans. In vertebrates, working memory is evident as a conserved alternating searching strategy. We can use automated tracking tools to measure this search strategy in Xenopus tadpoles. The free-movement pattern Y-maze assay is validated for assessing spatial working memory and cognitive flexibility in Xenopus. Deviations from randomness in search strategies are quantified by comparing relative alternating and repeating Y-maze arm entry choices within a 60-min time period in the maze. Pharmacologically or genetically abolishing working memory in these tadpoles disrupts their search strategy and adaptive behavior in a Y-maze arena, providing a valuable model to investigate intellectual disabilities and the architecture of cognition. In this chapter, we present our protocol for measuring working memory and locomotive ability in Xenopus using automated behavioral tracking equipment along with our recommended sample collection procedure for genotyping. We routinely use this protocol to investigate neurodevelopmental phenotypes, providing in vivo functional evidence to support patient diagnoses for novel disorders such as those affecting GRIA1 and DDX17.