Capturing the neural signature of the paraventricular thalamus that underlies individual variability in cue-motivated behavior

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Individuals make choices and prioritize actions using complex processes that assign value to rewards and associated stimuli based on prior experience. In our modern environment, we are surrounded by an abundance of stimuli that fight for our attention and often hinder goal-directed behavior. Stimuli, or cues in our environment, attain control over behavior via Pavlovian learning, such that previously neutral stimuli that predict reward acquire motivational properties and are thereby transformed into attractive and desirable incentive stimuli. Whether a stimulus acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Across species, individuals vary in the degree to which reward cues bias choice and control behavior. The neural processes that underlie this individual variation, however, remain to be determined. In the proposed studies we will exploit natural variation in cue-motivated behavior in rats and employ novel tools to identify critical components of the underlying neural circuitry. When rats are exposed to a Pavlovian conditioned approach paradigm, some, termed “goal-trackers”, primarily attribute predictive value to a discrete food-associated cue; whereas others, termed “sign-trackers” also attribute incentive salience to the cue. This animal model, therefore, allows us to dissociate the neural processes that promote predictive vs. incentive learning and the resultant behaviors. Using this model, the paraventricular nucleus of the thalamus (PVT) has emerged as a key node that acts to integrate input from top-down cortical control centers and bottom-up subcortical arousal centers and, in turn, guide cue-motivated behavior. Specifically, recent research from the PI’s laboratory suggests that sign-tracking behavior manifests when subcortical input to the PVT is weighed more heavily than cortical input. Thus, stimulation of cortical input to the PVT attenuates sign-tracking behavior, and this presumably occurs by shifting the control from bottom-up to top-down processes. The neural code within the PVT that reflects the integrated input and results in goal-directed or maladaptive behaviors remains to be determined and will be the focus of the current proposal. Fluorescence-based calcium imaging will be used in conjunction with machine-learning based “deep phenotyping” to determine the neural signature of the PVT that predicts subsequent cue-motivated behavior and underlies individual variation. In addition, “top-down” input from the prelimbic cortex to the PVT will be stimulated using chemogenetics and the resultant neuronal activity in the PVT and brain-behavior relationship will be assessed. These studies will generate a pipeline that future studies will rely on to more deeply probe the neural circuits by which stimuli in the environment attain control over, and incite, behavior.