The dynamic strategy shifting task: Optimisation of an operant task for assessing cognitive flexibility in rats

Area of Science:

• Neuroscience
• Cognitive Science
• Animal Models

Background:

• Cognitive dysfunction, particularly impaired cognitive flexibility and executive function, strongly predicts functional outcomes in schizophrenia.
• Current antipsychotic medications are ineffective in improving these cognitive deficits.
• Developing effective precognitive medications for schizophrenia has faced significant challenges in clinical trials.

Purpose of the Study:

• To optimize a novel dynamic strategy shifting task (DSST) for assessing cognitive flexibility in rats.
• To investigate the optimal stimuli and training parameters for the DSST, aiming to reduce extensive training times.
• To evaluate the effects of ketamine on cognitive flexibility using the DSST as a proof of concept.

Main Methods:

• Developed and optimized a dynamic strategy shifting task (DSST) using standard operant chambers.
• Trained 84 Sprague Dawley rats on the DSST, incorporating dynamic shifts between spatial and non-spatial rules.
• Administered acute doses of ketamine (0, 3, 10 mg/kg) and assessed cognitive flexibility via within-subject design, measuring premature and perseverant responses.

Main Results:

• Optimal learning in the DSST involved dynamic strategy shifts between spatial and non-spatial rules, with a minimum of 6 consecutive correct responses for within-session strategy changes.
• Ketamine administration resulted in fewer premature and more perseverant responses, indicating altered cognitive flexibility.
• Ketamine significantly improved performance on the reversal of a non-spatial visual discrimination rule, but not on spatial visual or response discrimination rules.

Conclusions:

• The DSST is a novel, rapid, and adaptable assay for studying distinct forms of cognitive flexibility and assessing the ability to shift between rule conditions.
• The DSST has potential utility in advancing the understanding of cognitive processes and neurobiological mechanisms related to flexibility in neuropsychiatric and neurological disorders.
• Findings suggest that the DSST can be used to investigate the effects of pharmacological agents on cognitive flexibility, with potential implications for developing treatments for executive dysfunction.