The prelimbic cortex and subthalamic nucleus contribute to cue-guided behavioral switching

• Contralateral disconnection of PL cortex and STN impairs behavioral switching.
• Contralateral disconnection of PL cortex and STM increases switch and perserverative errors.
• PL cortex inactivation biases rats to use an ineffective response strategy.
• NMDA receptor blockade in STN increases switch and perserverative errors.

Frontal cortex–basal ganglia circuitry supports behavioral switching when a change in outcome information is used to adapt response patterns. Less is known about whether specific frontal cortex–basal ganglia circuitry supports behavioral switching when cues signal that a change in response patterns should occur. The present experiments investigated whether the prelimbic cortex and subthalamic nucleus in male Long-Evans rats supports cue-guided switching in a conditional discrimination test. Rats learned in a cross-maze that a start arm cue (black or white) signaled which of two maze arms to enter for a food reward. The cue was switched every 3–6 trials. Baclofen and muscimol infused into the prelimbic cortex significantly impaired performance by increasing switch trial errors, as well as trials immediately following a switch trial (perseveration) and after initially making a correct switch (maintenance error). NMDA receptor blockade in the subthalamic nucleus significantly impaired performance by increasing switch errors and perseveration. Contralateral disconnection of these areas significantly reduced conditional discrimination performance by increasing switch and perseverative errors. These findings suggest that the prelimbic area and subthalamic nucleus support the use of cue information to facilitate an initial switch away from a previously relevant response pattern.