A Simple Spatial-independent Associative and Reversal Learning Task in Mice

The ability to adapt one's behavior in response to changing circumstances, or cognitive flexibility, is often altered in neuropsychiatric and neurodevelopmental conditions. In rodents, cognitive flexibility is frequently assessed using associative learning paradigms with a reversal component. The majority of existing protocols rely on unrestrictive exploration with no discouragement of wrong responses and are often influenced by spatial cues, at least during the test's learning phase. Here, we present a rewarded contingency discrimination learning test that minimizes the task's spatial component and contains an element that actively discourages pure exploratory responses. The method described herein is a manual version that can be performed using home-made equipment, but the test setup is amenable to automatization and can be adapted to address more complex cognitive demands, including conditional associative learning, attentional set formation, and attention shifting.