The social and communication impairments in individuals with autism spectrum disorders may be compounded by additional difficulties with executive functions. Children 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). Our laboratory is interested in examining analogous cognitive deficits in mouse models of autism. 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 (Brigman et al., 2005; Bussey et al., 2001).
Objectives:
Our long term objective is to investigate the hypothesis that the social and communication deficits in autism are related to cognitive disabilities. Impaired generalization (Stokes and Baer, 1977), deficits in cognitive flexibility or set shifting (Hughes et al., 1994; Ozonoff et al., 2004; Verte et al., 2006), and dysfunctional relational learning (Solomon et al., 2011) have been reported in autistic children and adults. A new technology, touch screen-based operant equipment for mice, incorporates capabilities for probing higher cortical functioning. The objective of the present experiments was to design and develop sophisticated touch screen cognitive tasks for mice. Our approach is based on the existing literature, using earlier equipment, for analogous tasks to measure executive functions mediated by the frontal cortex. Using novel methodologies for mice that parallel methods and equipment used in humans, we seek to understand complex cognitive capabilities of mice with genetic mutations associated with autism. To begin this endeavor, we employed the standardized inbred strain BTBR T+tf/J (BTBR) mouse model of autism, which displays social, communication, and repetitive behavioral abnormalities (Yang et al., 2009; Scattoni et al., 2011; Silverman et al., 2010).
Methods:
BTBR and C57BL/6J (B6) control mice were trained on a visual discrimination learning task and its reversal, as a measure of cognitive flexibility which involves inhibition of prepotent responses. Learning was assessed in touch screen-based operant equipment as described previously for mice (Brigman et al., 2008; Izquierdo et al., 2006) using commercially available touch screen chambers (Bussey-Saksida touch screen chamber for mice, Campden Instruments, UK) and its associated software (AbetII, Lafayette Instruments).
Results:
Our preliminary results indicate that BTBR are similar to B6 during the early shaping and training phases of the operant task. However, BTBR displayed slower initial discrimination learning compared to B6 control mice. Reversal learning is in progress. More complex tasks, including a relational learning task, are being designed and tested for validity for future use in BTBR and mutant mouse models.
Conclusions:
Here we provide preliminary data on the feasibility of operant touch screen tasks to measure cognitive flexibility in mice, using methods and equipment that are more closely analogous to procedures used in humans. We envision the automated touch screen system as a new research tool for exploring higher cognitive functions relevant to social cognition in mouse models of autism.