The long-term goal of our research program is to understand the impact of stressful events on sleep, and, in turn, how alterations in sleep are related to the persisting effects of stress. Stressors and conditioned/learned reminders of stressors can produce significant alterations in behavior and sleep. These alterations may vary with the intensity and controllability of the stressor and whether a successful coping strategy was developed. At the neurobiological level, the alterations may involve CRH in limbic regions implicated in stress and emotion, and in the control of arousal. However, the relationship between stress-induced behaviors and alterations in sleep, and their behavioral and neurobiological bases, are poorly understood. In this project, we intend to determine how variations in stressor intensity and controllability can influence post-stress sleep, and we intend to determine the role of CRH and CRH-related neuropeptides in the amygdala in regulating arousal and stress- induced alterations in sleep. Lastly, we will determine whether amygdalar modulation of stress-induced changes in arousal is associated with alterations in activity in brain regions implicated in stress and in brainstem monoaminergic cell groups that have been linked to the regulation of sleep and stress. To accomplish the objectives of this application we will: 1) determine the role(s) of stressor intensity and controllability in the effects of stress on sleep and behavior, 2) determine the role(s) of CRH1 and CRH2 receptors in the amygdala in regulating arousal and sleep, 3) determine the role(s) of CRH1 and CRH2 receptors in the amygdala in stress-induced alterations in arousal and sleep, and 4) we will identify regions involved in stress and in stress-induced alterations in rapid eye movement sleep, the sleep state that may be most impacted by stress. We will also measure heart and respiratory rate and plasma markers of the stress response. Understanding the neurobiology underlying the changes in sleep induced by controllable and uncontrollable stress should increase our understanding of how stress and stress-related emotion affect sleep and, in turn, the role altered sleep may play in the development of stress-related pathology. Such understanding may provide insight into sleep disorders such as insomnia and into emotional disorders in which sleep is affected. It will be especially relevant for insight into posttraumatic stress disorder (PTSD), which is characterized by disturbed sleep after a psychologically traumatic stressor.

Public Health Relevance

The goal or this research is to understand the impact of stressful events on sleep, and, in turn, how alterations in sleep are related to the persisting effects of stress. Stressors and even conditioned reminders of stressors can produce significant alterations in behavior and sleep. It is known that the effects of stressor intensity and controllability are important factors in the long-term effects of stress. However, it is not know how these factors impact sleep, or what role altered sleep may play in the long-term effects of stress. We will determine how stressor intensity and controllability affect post-stress sleep, and we will examine the role of corticotropin releasing hormone in the amygdala, a center of emotion in the brain, in regulating post-stress sleep. The insight provided by these studies may lead to improved treatments for sleep disorders such as insomnia and into emotional disorders in which sleep is affected. It will be especially relevant for understanding and potential treatment of posttraumatic stress disorder (PTSD), which is characterized by disturbed sleep after a psychologically traumatic stressor.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH064827-10
Application #
8259805
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (03))
Program Officer
Vicentic, Aleksandra
Project Start
2001-09-28
Project End
2013-09-25
Budget Start
2012-05-01
Budget End
2013-09-25
Support Year
10
Fiscal Year
2012
Total Cost
$319,646
Indirect Cost
$96,896
Name
Eastern Virginia Medical School
Department
Pathology
Type
Schools of Medicine
DUNS #
058625146
City
Norfolk
State
VA
Country
United States
Zip Code
23501
Wellman, Laurie L; Fitzpatrick, Mairen E; Machida, Mayumi et al. (2014) The basolateral amygdala determines the effects of fear memory on sleep in an animal model of PTSD. Exp Brain Res 232:1555-65
Britten, Richard A; Davis, Leslie K; Jewell, Jessica S et al. (2014) Exposure to mission relevant doses of 1 GeV/Nucleon (56)Fe particles leads to impairment of attentional set-shifting performance in socially mature rats. Radiat Res 182:292-8
Wellman, Laurie L; Yang, Linghui; Ambrozewicz, Marta A et al. (2013) Basolateral amygdala and the regulation of fear-conditioned changes in sleep: role of corticotropin-releasing factor. Sleep 36:471-80
Machida, Mayumi; Yang, Linghui; Wellman, Laurie L et al. (2013) Effects of stressor predictability on escape learning and sleep in mice. Sleep 36:421-30
Dong, Enheng; Wellman, Laurie L; Yang, Linghui et al. (2012) Effects of microinjections of Group II metabotropic glutamate agents into the amygdala on sleep. Brain Res 1452:85-95
Zeng, Tao; Mott, Christopher; Mollicone, Daniel et al. (2012) Automated determination of wakefulness and sleep in rats based on non-invasively acquired measures of movement and respiratory activity. J Neurosci Methods 204:276-87
Yang, L; Wellman, L L; Tang, X et al. (2011) Effects of corticotropin releasing factor (CRF) on sleep and body temperature following controllable footshock stress in mice. Physiol Behav 104:886-92
Liu, Xianling; Wellman, Laurie L; Yang, Linghui et al. (2011) Antagonizing corticotropin-releasing factor in the central nucleus of the amygdala attenuates fear-induced reductions in sleep but not freezing. Sleep 34:1539-49
Yang, Linghui; Wellman, Laurie L; Ambrozewicz, Marta A et al. (2011) Effects of stressor predictability and controllability on sleep, temperature, and fear behavior in mice. Sleep 34:759-71
Sanford, Larry D; Yang, Linghui; Wellman, Laurie L et al. (2010) Differential effects of controllable and uncontrollable footshock stress on sleep in mice. Sleep 33:621-30

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