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.

Public Health Relevance

The proposed research is relevant to public health because sleep is required for good health and affects human cognitive performance and productivity. Animal research is needed because it is not possible to carry out brain mechanisms of sleep experiments in humans. However, unlike human sleep loss experiments, all current animal sleep loss methods use forced aversive stimuli. The ability to delineate the effects of those aversive stimuli from the effects specific to sleep loss using current animal sleep deprivation methods is severely limited. This proposal addresses this critical issue by developing animal models where sleep loss is rewarding and self-selected thereby avoiding the complexities associated with aversive stimuli and loss of control of one's environment that are inherent in animal sleep deprivation models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS085605-01A1
Application #
8822760
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
He, Janet
Project Start
2014-09-30
Project End
2016-07-31
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$219,984
Indirect Cost
$69,984
Name
Washington State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164