Locus Coeruleus Activity during Sleep Deprivation

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

DESCRIPTION (provided by applicant): The project proposed in this application is designed to test how 43 hours sleep deprivation (SD) alters performance and locus coeruleus (LC) activity in rhesus monkeys engaged in a task requiring sustained and selective attention. The first goal is to validate the rhesus monkey as an animal model to explore the neurophysiology of cognition during SD. The LC is the primary source of cerebral norepinephrine and its activity is known to contribute both to attentional processes and arousal-state control. Most theoretical accounts for the impact of SD on behavior claim (or imply) that changes in LC and norepinephrine actively modulate the arousal-limited cognitive resources necessary for performance. This project will provide the first empirical test of that assumption with a design that samples performance and LC activity every 3 hours, sufficient temporal sampling to track the influence of both homeostatic and circadian pressures on performance. Human performance during SD shows increases in reaction time and error rate that is modulated by circadian phase. Sleep deprived human performance becomes highly variable, revealing both non-responsiveness and moments of near-normal performance. To test if SD results in degraded or compensatory LC activity, baseline and task-related LC neuronal firing will be evaluated as a function of time awake during 43 hours without sleep. The ability for exogenous auditory stimulation to activate the LC and/or improve performance as time awake increases will also be tested. This project assimilates validated methods of cognitive testing in primates, electrophysiologic LC recording, and monkey sleep deprivation in an experiment designed to provide original data measuring how SD alters brain activity critical for cognition.