Flexible behavior is associated with stronger inputs from the mediodorsal thalamus to the orbitofrontal cortex

Behavioral flexibility is the ability to adapt behavior when facing environmental changes. This function typically involves the cognitive circuitry of the basal ganglia, which receives inputs from frontal cortical areas. Here, we investigated the role of the orbitofrontal cortex (OFC) and its thalamic inputs in behavioral flexibility. This study combined behavioral approaches and in vivo electrophysiology in anesthetized rats. First, we assessed flexibility with a set-shifting task. This procedure alternates between visual discrimination rules and response discrimination rules. An individual inflexibility score was calculated based on behavioral performance. Rats were then categorized into flexible, intermediate and inflexible groups. Next, we used in vivo juxtacellular recordings to assess spontaneous firing from OFC neurons in flexible and inflexible rats. We also evaluated the strength of two thalamocortical inputs with electrical stimulation of mediodorsal (MD) or submedius (Sub) thalamic nuclei. Our results suggest that flexible rats exhibit a higher density of spontaneously active neurons in the OFC. Moreover, MD stimulation was more efficient in flexible rats, whereas Sub stimulation failed to evoke a spike in both groups. To further explore the MD-OFC projection, evoked local field potentials (LFP) were recorded in the OFC and a high frequency stimulation (HFS) protocol was applied to the MD-OFC pathway. Following HFS, the LFP amplitude increased significantly in flexible rats, displaying a long-term potentiation whereas inflexible rats exhibited no change following HFS. Altogether, these results suggest that the level of engagement of OFC by MD inputs might contribute to individual behavioral flexibility performances.