Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure.

The medial prefrontal cortex (mPFC) of the rat plays an essential role in behavioral flexibility, as lesions or inactivations of this region impair shifting between strategies or attentional sets using a variety of different behavioral tests. In the present study, we assessed the effects of inactivation of the mPFC on strategy set-shifting and reversal learning, using a novel, automated procedure conducted in an operant chamber. In Experiment 1, inactivation of the mPFC with bupivacaine did not impair the initial learning of a visual-cue (i.e.; always press the lever with a cue light illuminated above it) or a response (i.e.; always press the left lever) discrimination. Control rats required greater number of trials to shift from using a visual-cue to a response strategy than the opposite shift. mPFC inactivation impaired performance of a visual-cue-response set-shift, but not the easier response-visual-cue shift. In Experiment 2, pre-exposure to the visual-cue stimulus lights increased the difficulty of the response-visual-cue shift, reflected by a greater number of trials required by control rats to achieve criterion relative to those in Experiment 1. Under these conditions, inactivation of the mPFC did impair performance of this set-shift. In contrast, mPFC inactivation did not affect reversal learning of a response discrimination. These findings highlight the utility of this automated procedure for assessing set-shifting mediated by the mPFC. Furthermore, they reveal that the relative difficulty of the type of shift rats are required to perform has a direct impact on whether or not the mPFC contributes to this form of behavioral flexibility.

Thalamic-prefrontal cortical-ventral striatal circuitry mediates dissociable components of strategy set shifting.

The mediodorsal nuclei of thalamus (MD), prefrontal cortex (PFC), and nucleus accumbens core (NAc) form an interconnected network that may work together to subserve certain forms of behavioral flexibility. The present study investigated the functional interactions between these regions during performance of a cross-maze-based strategy set-shifting task. In Experiment 1, reversible bilateral inactivation of the MD via infusions of bupivacaine did not impair simple discrimination learning, but did disrupt shifting from response to visual cue discrimination strategy, and vice versa. This impairment was due to an increase in perseverative errors. In Experiment 2, asymmetrical disconnection inactivations of the MD on one side of the brain and PFC on the other also caused a perseverative deficit when rats were required to shift from a response to a visual cue discrimination strategy, as did disconnections between the PFC and the NAc. However, inactivation of the MD on one side of the brain and the NAc contralaterally resulted in a selective increase in never-reinforced errors, suggesting this pathway is important for eliminating inappropriate strategies during set shifting. These data indicate that set shifting is mediated by a distributed neural circuit, with separate neural pathways contributing dissociable components to this type of behavioral flexibility.