Abstract
Repetitive behaviors are a key feature of many pervasive developmental disorders, such as autism. As a heterogeneous group of symptoms, repetitive behaviors are conceptualized into two main subgroups: sensory/motor (lower-order) and cognitive rigidity (higher-order). Although lower-order repetitive behaviors are measured in mouse models in several paradigms, so far there have been no high-throughput tests directly measuring cognitive rigidity. We describe a novel approach for monitoring repetitive behaviors during reversal learning in mice in the automated IntelliCage system. During the reward-motivated place preference reversal learning, designed to assess cognitive abilities of mice, visits to the previously rewarded places were recorded to measure cognitive flexibility. Thereafter, emotional flexibility was assessed by measuring conditioned fear extinction. Additionally, to look for neuronal correlates of cognitive impairments, we measured CA3-CA1 hippocampal long term potentiation (LTP). To standardize the designed tests we used C57BL/6 and BALB/c mice, representing two genetic backgrounds, for induction of autism by prenatal exposure to the sodium valproate. We found impairments of place learning related to perseveration and no LTP impairments in C57BL/6 valproate-treated mice. In contrast, BALB/c valproate-treated mice displayed severe deficits of place learning not associated with perseverative behaviors and accompanied by hippocampal LTP impairments. Alterations of cognitive flexibility observed in C57BL/6 valproate-treated mice were related to neither restricted exploration pattern nor to emotional flexibility. Altogether, we showed that the designed tests of cognitive performance and perseverative behaviors are efficient and highly replicable. Moreover, the results suggest that genetic background is crucial for the behavioral effects of prenatal valproate treatment.
Highlights
Along with impairments of social interactions and communication, the most characteristic symptoms of autism are the repetitive behaviors (American Psychiatric Association, 2013)
IMPAIRMENT OF REWARD MOTIVATED PLACE LEARNING IS MUCH STRONGER IN VALPROATE-TREATED BALB/c THAN C57BL/6 MICE Cognitive performance of C57BL/6 and BALB/c valproate-treated mice was assessed during place preference and place reversal learning
Comparison of C57BL/6 and BALB/c control mice revealed differences in the performance level www.frontiersin.org related to light-dark cycle similar to those observed during place preference learning (Figure S2B)
Summary
Along with impairments of social interactions and communication, the most characteristic symptoms of autism are the repetitive behaviors (American Psychiatric Association, 2013). Restricted, repetitive patterns of behavior, interests or activities manifested as, e.g., resistance to change learned response, result in cognitive rigidity (Lopez et al, 2005). Autism is diagnosed with accompanying intellectual impairment (American Psychiatric Association, 2013), with cognitive deficits unrelated to repetitive or restricted behaviors. It remains unclear whether reversal learning impairment that accompanies autism is caused by increased perseveration or by specific cognitive deficits, as the available behavioral tasks do not usually allow for a simultaneous assessment of perseveration and cognitive performance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
