The mediodorsal thalamus supports adaptive responding based on stimulus-outcome associations.

The ability to engage into flexible behaviors is crucial in dynamic environments. We recently showed that in addition to the well described role of the orbitofrontal cortex (OFC), its thalamic input from the submedius thalamic nucleus (Sub) also contributes to adaptive responding during Pavlovian degradation. In the present study, we examined the role of the mediodorsal thalamus (MD) which is the other main thalamic input to the OFC. To this end, we assessed the effect of both pre- and post-training MD lesions in rats performing a Pavlovian contingency degradation task. Pre-training lesions mildly impeded the establishment of stimulus-outcome associations during the initial training of Pavlovian conditioning without interfering with Pavlovian degradation training when the sensory feedback provided by the outcome rewards were available to animals. However, we found that both pre- and post-training MD lesions produced a selective impairment during a test conducted under extinction conditions, during which only current mental representation could guide behavior. Altogether, these data suggest a role for the MD in the successful encoding and representation of Pavlovian associations.

Targeting Reciprocally Connected Brain Regions Through CAV-2 Mediated Interventions.

An important issue in contemporary neuroscience is to identify functional principles at play within neural circuits. The reciprocity of the connections between two distinct brain areas appears as an intriguing feature of some of these circuits. This organization has been viewed as "re-entry," a process whereby two or more brain regions concurrently stimulate and are stimulated by each other, thus supporting the synchronization of neural firing required for rapid neural integration. However, until relatively recently, it was not possible to provide a comprehensive functional assessment of such reciprocal pathways. In this Brief Research Report, we highlight the use of a chemogenetic strategy to target projection-defined neurons in reciprocally connected areas through CAV-2 mediated interventions in the rat. Specifically, we targeted the bidirectional pathways between the dorsomedial prefrontal cortex (dmPFC) and the mediodorsal thalamus, as well as those connecting the insular cortex (IC) and the basolateral complex of the amygdala (BLA). These data showcase the usefulness of CAV-2-related strategies to address circuit-level issues. Moreover, we illustrate the inherent limitation of Cre-dependent adeno-associated virues (AAVs) with "leaked" expression of the gene of interest in the absence of Cre and highlight the need for appropriate control conditions.