Cognitive Abilities on Transitive Inference Using a Novel Touchscreen Technology for Mice

Cognitive abilities are impaired in neurodevelopmental disorders, in-cluding autism spectrum disorder (ASD) and schizophrenia. Preclini-cal models with strong endophenotypes relevant to cognitive dysfunctions offer a valuable resource for therapeutic development. However, improved assays to test higher order cognition are needed. We employed touchscreen technology to design a complex transitive inference (TI) assay that requires cognitive flexibility and relational learning. C57BL/6J (B6) mice with good cognitive skills and BTBR T +tf/J (BTBR), a model of ASD with cognitive deficits, were evalu-ated in simple and complex touchscreen assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR displayed deficits on components of TI, when 4 stimuli pairs were interspersed, which required flexible integrated knowledge. BTBR displayed impairment on the A> E inference, analogous to the A> E deficit in ASD. B6 and BTBR mice both reached criterion on the B> D comparison, unlike the B> D impairment in schizophrenia. These results demon-strate that mice are capable of complex discriminations and higher order tasks using methods and equipment paralleling those used in humans. Our discovery that a mouse model of ASD displays a TI deficit similar to humans with ASD supports the use of the touchsc-reen technology for complex cognitive tasks in mouse models of neurodevelopmental disorders