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The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice
Published on: February 4, 2015
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Training Mice to Perform Attentional Set-Shifting Under Head Restraint
Katarina Kalajzic1, John J Stout2, Alexander C Mitchell2
1Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
Bio-Protocol
|September 15, 2025
Summary
This study presents a novel head-restrained rodent model for measuring cognitive flexibility using an attentional set-shifting paradigm. This method allows for simultaneous behavioral and neural activity analysis, advancing research into neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Cognitive Science
- Behavioral Science
Background:
- Cognitive flexibility, the ability to adapt behavior to changing rules, is crucial for goal-directed actions.
- Attentional set-shifting paradigms, like the Wisconsin Card Sorting Test, assess this ability but are challenging to translate to rodents.
- Disruptions in cognitive flexibility are implicated in neuropsychiatric disorders such as schizophrenia and Alzheimer's disease.
Purpose of the Study:
- To develop and validate a head-restrained attentional set-shifting paradigm in mice.
- To enable simultaneous behavioral and neural recordings for studying cognitive flexibility mechanisms.
- To provide a translational tool for investigating cognitive deficits in rodent models of neuropsychiatric disorders.
Main Methods:
- A head-restrained paradigm was designed for water-restricted mice, utilizing odor or whisker vibration cues.
- Mice learned to associate cues with directional lick responses for water rewards, adapting to periodically switching stimulus-response-outcome rules.
- The paradigm was integrated with 2-photon calcium imaging, optogenetics, and electrophysiology for concurrent neural and behavioral measurements.
Main Results:
- The head-restrained setup successfully allowed mice to perform the attentional set-shifting task, demonstrating cognitive flexibility.
- The paradigm facilitated precise control over stimuli, responses, and outcomes, enabling detailed behavioral analysis.
- Integration with neural recording techniques allowed for the examination of neural correlates of cognitive flexibility.
Conclusions:
- This head-restrained attentional set-shifting paradigm offers a robust and versatile method for studying cognitive flexibility in rodents.
- It serves as a valuable tool for investigating the neural circuitry underlying cognitive flexibility and its dysfunction in neuropsychiatric conditions.
- The paradigm's compatibility with advanced neurophysiological techniques opens new avenues for translational research in brain disorders.

