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Reversal learning in C58 mice: Modeling higher order repetitive behavior.

Cristina M Whitehouse1, Lisa S Curry-Pochy2, Robin Shafer1

  • 1Department of Psychiatry, University of Florida, McKnight Brain Institute, 1149 Newell Drive, L4-100, Gainesville, FL 32611, USA.

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The C58 mouse model displays autism-related repetitive behaviors and resistance to change. Environmental enrichment improved their reversal learning, enhancing its translational value for autism research.

Keywords:
Autism spectrum disordersEnvironmental enrichmentNeurodevelopmental disordersResistance to changeStereotypy

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Area of Science:

  • Neuroscience
  • Behavioral Science
  • Genetics

Background:

  • Restricted, repetitive behaviors (RRBs) are core diagnostic features of autism spectrum disorder (ASD) and other neurodevelopmental disorders.
  • RRBs manifest as repetitive sensory-motor actions and resistance to change.
  • The C58 mouse strain exhibits high rates of aberrant repetitive sensory-motor behaviors, making it a potential model for RRBs.

Purpose of the Study:

  • To further characterize the C58 mouse strain as a model for autism by assessing its resistance to change.
  • To compare the C58 mouse strain to the C57BL/6 strain on a reversal learning task.
  • To investigate the impact of environmental enrichment on the C58 mouse model's performance.

Main Methods:

  • C58 and C57BL/6 mice were compared using a reversal learning task.
  • Two reinforcement schedules were employed: 100% and 80%/20% probabilistic.
  • The effect of environmental enrichment on task performance was evaluated.

Main Results:

  • No significant strain differences were observed under the 100% reinforcement schedule.
  • Under the probabilistic schedule, C58 mice showed no deficit in acquisition but were impaired in reversal learning compared to controls.
  • Environmental enrichment did not affect acquisition but significantly improved reversal learning in C58 mice.

Conclusions:

  • C58 mice exhibit both repetitive sensory-motor behaviors and resistance to change, mirroring key aspects of autism.
  • Environmental enrichment attenuates both clusters of repetitive behaviors in the C58 model.
  • These findings enhance the translational validity of the C58 mouse strain for studying autism and related neurodevelopmental disorders.