Touchscreen learning of transitive inference in B6 mice and the BTBR mouse model of autism
Saturday, Nov 09, 2013, 1:00 PM - 2:00 PM
++C.07.a. Autism: Genetic and animal models
*J. L. SILVERMAN
, P. T. GASTRELL
, M. C. PRIDE
, J. E. HAYES
, M. SOLOMON
, J. N. CRAWLEY
UC Davis Sch. of Med., Sacramento, CA;
Lab. of Behavioral Neurosci., Natl. Inst. of Mental Hlth., Bethesda, MD
Intellectual impairments are a primary symptom of many neurodevelopmental disorders, and an associated symptom of autism. Individuals on the autism spectrum often show intact learning on simple tasks but display deficits on aspects of inhibitory control, cognitive flexibility, and relational learning tasks as compared with age matched controls (Christ et al., 2011; Solomon et al., 2008; Solomon et al., 2011). Emerging literature indicates that mice are capable of complex visual discriminations and higher order tasks using methods and operant equipment that are similar to those used in humans and non-human primates (Bussey et al., 2001; Brigman et al., 2005). Operant touchscreen equipment for mice incorporates capabilities to probe higher cortical functioning. The present experiments describe a sophisticated touchscreen task of transitive inference (TI) for mice that requires inhibitory control, cognitive flexibility and relational learning. To evaluate mice in a touchscreen version of TI, we assessed performance in an inbred strain of mice with generally normal cognitive abilities, C57BL6/J (B6), and in a mouse model of autism, BTBR T+tf/J (BTBR), which displays deficits on cognitive tasks including fear conditioning, water maze, and novel object recognition (MacPherson et al., 2008; Yang et al., 2012b; Rutz and Rothblat, 2012; Silverman et al. 2013). Both strains were first evaluated on a standard task of pairwise visual discrimination and reversal learning (Brigman et al., 2008; Brigman and Rothblat, 2008; Brigman et al., 2010a; Rutz and Rothblat, 2012). Another cohort of each strain was evaluated during serial training of the premise pairs (the A > B, B > C, C > D, D > E sequence) and integrated retention tests. At the end of training, both strains were given the TI probe test for the B > D transitive inference, and the A > E end pair, a simpler inference. BTBR and B6 performed similarly on pairwise visual discrimination and reversal. BTBR displayed deficits on components of TI, specifically when four premise pairings were interspersed during inference training retention tests, which require more complex, flexible integration of knowledge. B6 and BTBR mice both reached criterion on the B > D comparison. Performance by BTBR was worse than B6 on the end paired A > E. Impaired performance on only the A > E pairing has been reported in adults with autism spectrum disorders (Solomon et al., 2011). Our data demonstrate that mice are capable of complex visual discriminations and higher order TI tasks using methods and equipment similar to those used in humans and non-human primates, and that deficits may be detectable in mouse models of autism using the touchscreen technology.
National Institute of Mental Health Intramural Research Program
MIND Institute, University of California Davis School of Medicine
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