Contributions of the Prelimbic Cortex and Basal Ganglia Circuitry to Proactive Behavioral Switching

Frontal cortex- basal ganglia circuitry supports behavioral switching when a change in outcome information is used to shift strategies. Less is known about whether specific frontal cortex-basal ganglia circuitry supports proactive switching when cues signal that a change in strategies should occur. The present experiments investigated whether the prelimbic cortex and its connections with two basal ganglia structures, the subthalamic nucleus, and the dorsomedial striatum in male Long-Evans rats supports proactive switching between visual cue-place associations. In a cross-maze, rats learned a conditional discrimination in which a start arm cue (black or white) signaled which one of two maze arms to enter for a food reward. The cue was switched every 3-6 trials. In the first set of experiments, 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 proactive switching accuracy by increasing switch and perseverative errors. These findings suggest that the prelimbic area and subthalamic nucleus support the use of cue information to facilitate inhibition of a previously relevant response pattern. In the second set of experiments, results of prelimbic cortex inactivation were confirmed in a second group of animals. Additionally, NMDA receptor blockade in the dorsomedial striatum resulted in an increase in switch, perseverative, and maintenance errors due to an increase in the likelihood of a rat to miss an entire block of trials. Contralateral disconnection of the prelimbic and dorsomedial striatal areas also increased all errors because of an increase in missed blocks of trials. These results suggest that the prelimbic cortex and dorsomedial striatum support the use of cue information to select and maintain a strategy throughout a block of trials. Overall, results from both sets of experiments suggest that the prelimbic cortex interacts with both the subthalamic nucleus and dorsomedial striatum in a top-down manner to execute proactive switches in behavior when cues guide strategy switches.