Individual differences in sleep-related neural dynamics in sign trackers vs goal trackers

项目摘要/摘要

PROJECT SUMMARY / ABSTRACT In humans, altered sleep is associated with an increased risk of alcohol and substance abuse disorders in some select individuals. This presents a chicken and the egg problem that is often difficult to answer in clinical populations: do the sleep differences in these individuals represent an underlying sleep architecture that promotes addictive behavior, or are the sleep disturbances caused by the consumption of drugs or alcohol? Here, we use and extend a preclinical model to understand the relationship between sleep deprivation and reward-seeking behaviors. There are individual differences in the motivational states that are triggered by reward-related cues, with some individuals experiencing stronger feelings of desire and craving (i.e. incentive salience) when exposed to a cue than others. These individual differences can be modeled in rodents using a Pavlovian Conditioned Approach (PCA) procedure, in which a discrete and localizable cue is paired with food reward. When the cue is available, some rats will approach and interact with it (“sign trackers”, STs); whereas other rats will approach the site of food delivery (“goal trackers”, GTs). The differences between STs and GTs represent stable behavioral traits that are largely genetically determined, and are associated with differences in other psychological (e.g. impulsivity) and neurobiological (e.g. altered dopaminergic activity) features. Our central hypothesis is that sleep deprivation differentially impacts reward-related learning in different individuals. In Aim 1, we will causally test this hypothesis by sleep-depriving a very large number of male and female rodents and asking how the disturbed sleep alters their reward-seeking behaviors in the PCA task. Our preliminary data show that sleep deprivation causes a remarkably robust increase in sign-tracking behavior with a clear loss of more nuanced, intermediate behaviors. In Aim 2, we will carry out massive-scale task- and sleep-related electrophysiological recordings simultaneously from multiple reward-related brain regions, including the nucleus accumbens, ventral pallidum, medial prefrontal cortex and hippocampus. Many of these areas are implicated in both motivational control and sleep regulation, making them ideal candidates to reveal correlated individual differences in incentive salience and sleep-related dynamics. The significance of this project is two-fold: we will establish the first preclinical model that relates sleep deprivation to individual differences in learning and reward-seeking; and secondly, by identifying neural signatures that differ across individuals with distinct reward-seeking phenotypes, this work can be translated into using sleep EEG to identify and help individuals who are prone to drug-seeking behavior or relapse.