OPERON (Papaleo-Scheggia’s method)

Application

Attentional set shifting is a measure of cognitive flexibility and executive functions, refering to the ability to switch between arbitrary internal rules (“cognitive-attentional sets”). The most widely used neuropsychological tasks for the
evaluation of this function in humans are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-Dimensional set-shifting task (ID/ED).

These tasks have been used to identify specific cognitive abnormalities in a wide range of mental disorders including autism, schizophrenia, Parkinson’s disease, obsessive-compulsive disorders, and attentiondeficit/hyperactivity disorders.

The clinical relevance and solid methodologic approach of the WCST and the ID/ED tests have attracted interest in preclinical research. Importantly, these tasks allow for the selective measurement of discriminative learning, reversal learning, and switching of attention within the same dimension (intradimensional shift [IDS]) and between different perceptual dimensions (extradimensional shift [EDS]) within the same subject. This distinction is crucial because a double dissociation or functional specialization between the lateral (in monkeys and humans)/medial (in rodents) and orbital regions of the prefrontal cortex (PFC) have been demonstrated. That is, whereas the orbitofrontal cortex is selectively involved in the reversal phases of these tasks, the lateral/medial PFC region governs the EDS stages.

This novel operant-based two-chamber ID/ED “Operon” task for mice is able to measure attentional set shifting in mice and the effects of genetic and pharmacologicmanipulations of dopamine and glutamate. In genetically modified mice with reduced catechol-O-methyltransferase activity there wasselective improvement on extradimensional shift abilities and impairment of serial reversal learning.

The instrument is composed of:

• A 2-compartment cage, each provided with an operant wall for automated tridimensional stimulation, and an innovative Revolver System for automated tactile stimulation
• An Odor Delivery System providing 10 di?erent odors in 2 independent channels
• A specific version of ANY-maze software managing the test and collecting the data

Method Paper

• Diego Scheggia, Audrey Bebensee, Daniel R. Weinberger, and Francesco Papaleo: "The Ultimate Intra-/Extra-Dimensional Attentional Set-Shifting Task for Mice"  Biological Psychiatry, Volume 75, Issue 8, Pages 660-670, 15 April 2014 - https://doi.org/10.1016/j.biopsych.2013.05.021
• Diego Scheggia, Francesco Papaleo et alia: "Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment" Nat Commun. 2018 Jun 11;9(1):2265. doi: https://doi.org/10.1038/s41467-018-04711-w Erratum in: Nat Commun. 2018 Aug 29;9(1):3560