Identifying a neurochemical signature of the paraventricular nucleus of the thalamus that predicts individual variability in cue-reward learning

Abstract

To investigate neurochemical factors that may confer vulnerability to psychiatric disorders, we used an animal model that captures a transdiagnostically relevant neurobehavioral endophenotype. During a Pavlovian conditioned approach paradigm, rats learn the predictive relationship between a lever cue and food reward. A subset of rats, sign trackers, also attribute incentive motivational value to the lever cue. Relative to non sign trackers, STs are more impulsive, have attentional deficits, and show greater reinstatement of drug seeking behavior. The paraventricular nucleus of the thalamus is a key neural node implicated in these individual differences. We combined in vivo microdialysis with liquid chromatography tandem mass spectrometry to quantify 22 neurobiologically relevant small molecules in the PVT before and 24 hours after Pavlovian training. Before training, glucose concentrations in the paraventricular nucleus of the thalamus were higher in rats subsequently classified as sign trackers than in non sign trackers and were correlated with the Pavlovian conditioned approach index used to phenotype the rats. Glucose concentrations decreased after training, and the magnitude of change differed between phenotypes. Multivariate regression identified baseline neurochemical profiles in the paraventricular nucleus of the thalamus associated with subsequent Pavlovian conditioned approach behavior. These findings identify a candidate PVT neurochemical signature that precedes behavioral phenotyping and may mark the propensity to sign track, providing insight into potential mechanisms underlying vulnerability to psychiatric disorders characterized by maladaptive cue motivated behavior.