"Uncoupling sleep deprivation-associated stressors from sleep loss in rodents"

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DESCRIPTION (provided by applicant): Many conclusions about brain sleep mechanisms are derived from animal sleep deprivation (SD) experiments. However, SD in animals is induced by uncontrollable (from the animal's perspective) aversive stimuli used in animal SD studies. In contrast, sleep loss in human experiments is voluntary. The overall goal of this project is to use intracranial self-stimulation (ICSS) as a rewarding, self-chosen method for rodent SD in order to un- couple the effects of the uncontrollable aversive components inherent in current animal SD protocols from the effects of sleep loss per se. We will compare gentle handling SD (GH-SD) vs. ICSS-SD vs. imposed brain stimulation (NCS-SD) in rats using polysomnography, plasma levels of ACTH, corticosterone, and prolactin, and performance on a sustained attention task. Thus, we will isolate the contributions of volition and aversiveness in SD-methods on each measure. The objectives of Aim 1 are to compare rat EEG and endocrine responses in GH-SD, NCS-SD and ICSS-SD. Pilot data show that ICSS is an effective technique for SD. We test the hypotheses that; 1) compared to GH-SD, ICSS-SD and NCS-SD rats will show similar sleep rebound, and 2) plasma expression of stress biomarkers are elevated after GH-SD compared to NCS-SD and ICSS-SD. Our recent data indicate that post-GH-SD performance on the rat psychomotor vigilance task (rPVT) shows important discrepancies with human PVT data. We developed a new rodent attention task, the nRAT. The objectives of Aim 2 are to: 1) contrast nRAT performance after each SD-type; and 2) compare post-SD changes in performance to those from SD human PVT experiments. We test the hypothesis that compared to the other SD-types, ICSS-SD will result in performance deficits in the nRAT that are more representative of performance occurring after SD in the human PVT. The proposed experiments will distinguish between uncontrollable aversive stimuli-induced vs. sleep loss-induced EEG, endocrine and cognitive responses. This proposal is innovative because we: a) compare responses induced by both ICSS and GH-SD methods of SD, b) develop a new self-imposed animal method to induce sleep loss devoid of forced and aversive SD techniques, c) vary SD-types in the nRAT and compare results with human PVT; and d) validate the nRAT as a model of post-SD time-on-task decrements in humans. Anticipated results will provide a new rewarding self-administered SD method and a new cognitive rodent task for use in animal brain mechanism studies -- a long term goal of this project.