Impact of adolescent sleep and circadian disruption on cognition, reward processing, and cortical function

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

PROJECT SUMMARY PROJECT 4 Adolescence is a period of enhanced vulnerability to develop substance use disorders in part due to the ongoing development of neural circuits associated with reward and executive function (i.e., impulsivity, attention, reward sensitivity). In addition, adolescents experience a developmentally regulated shift in circadian rhythms to a more evening chronotype and have less perceived sleep drive. Thus, adolescents are biologically driven to stay up later at night and wake later in the morning. However, this natural shift in circadian rhythms is in conflict with societal norms, particularly early school start times, which can lead to a chronic state of circadian misalignment and insufficient sleep. The degree to which chronic circadian and sleep disturbances in adolescence impacts brain development and risk for drug abuse is not well understood. Moreover, there is a wide variation in the degree of circadian shift amongst adolescents, leading to the possibility that certain individuals are more at risk than others for circadian and sleep-associated dysfunction. Therefore, an increased understanding of the behavioral and neural consequences of sleep and circadian disturbances is needed to inform new interventions and preventative strategies. Project 4 of the Center for Adolescent Reward, Rhythms, and Sleep (CARRS) renewal aims to determine the neurocognitive effects of circadian misalignment in the absence of sleep loss (Aim 1) and chronic sleep disruption (Aim 2) on behavioral indices of addiction risk and cortical neural activity in adolescent rats. We will use integrated recordings of single unit neural activity and EEG while rats perform two different tasks to assess response inhibition impulsivity and attribution of incentive salience to reward-associated cues – the cued response inhibition task (CRIT) and Pavlovian conditioned approach (PA), respectively. The proposed experiments are informed by the results of CARRS-1, which found that circadian and sleep manipulations in human adolescents alter response inhibition and PFC function. In addition, in CARRS-1 we found that chronic circadian misalignment promotes drug self-administration, particularly for nicotine in adolescent rats; thus, Aim 3 will determine if molecular rhythm disruption, specifically in nucleus accumbens projecting prefrontal cortex neurons is sufficient to alter self-administration of nicotine or THC, or alter behavior in either of the cognitive tasks. Rats will be bred and undergo circadian and sleep manipulations under the direction of the Subject Management and Bio-banking Core B. Data analysis and storage will be supported by Data Management and Statistics Core C. Results of these studies will be integrated with human EEG and behavioral data obtained in Projects 1 and 2, and with the molecular and ex vivo electrophysiological results obtained in Projects 3 and 5.