Elucidating the Role of the Paraventricular Nucleus of the Thalamus in Cue-Motivated Behavior.

Abstract

Recently, there has been increased interest in the role of the paraventricular nucleus of the thalamus (PVT) in motivated behaviors, specifically in response to reward-paired cues. The precise role of the PVT in these behaviors has been difficult to identify since Pavlovian conditioned cues can act as both predictive and incentive stimuli. Using an animal model that captures individual variation in Pavlovian conditioned approach (PCA) behavior, these properties of stimulus-reward learning can be differentiated. When rats are exposed to a PCA paradigm, wherein presentation of a discrete cue predicts delivery of a food reward, some rats (goal-trackers; GTs) treat the cue exclusively as a reward predictor and approach the location of impending reward delivery upon cue presentation. Other rats (sign-trackers; STs) attribute both predictive and incentive value to the cue, and approach and engage the reward-paired cue upon presentation. STs will also work to a greater extent than GTs for cue presentation in the absence of reward, another measure of incentive salience attribution. Using this model, work from our laboratory has indicated that the PVT may play an important role in mediating the propensity to attribute incentive salience to reward cues. Here, I confirmed a role for the PVT in sign- and goal-tracking behavior through the use of pharmacological lesions. Next, I identified distinct populations of PVT efferents and afferents that are engaged following presentation of a predictive stimulus (i.e. for GTs) or one that is also attributed with incentive value (i.e. for STs). My work revealed that presentation of a predictive stimulus activates PVT afferents from the prelimbic cortex, while an incentive stimulus engages subcortical structures communicating with the PVT, including afferents from the lateral hypothalamus and efferents to the nucleus accumbens. Last, I used local pharmacology to demonstrate that blocking orexin-receptor 2 in the PVT attenuates sign-tracking behavior, indicating that this pathway is involved in the attribution of incentive salience to reward-paired cues. Taken together, this work has yielded a model in which the PVT is a central node between top-down processing, mediating goal-tracking behavior, and a sub-cortical drive that can override this top-down control, mediating sign-tracking behavior.