The overall goal of this proposal is to explore the processes underlying long-term habituation to repeated intermittent stress. Emotional stressors elicit a range of behavioral, autonomic, and endocrine responses that normally help organisms cope with challenging situations. However, prolonged or repeated exposure to stressful life events is frequently associated with several psychopathologies and physical disorders. Thus, habituation to stress is likely a vital mechanism allowing organisms to reduce the impact of repeatedly experienced stress situations. Unfortunately, the neural mechanisms specifically mediating normal stress habituation are unknown. Based on current evidence and preliminary studies, a model is proposed where the site of plasticity associated with habituation to stress is located at the interface between an auditory signaling pathway and a central effector region that controls many, if not all, responses normally associated with stress.
Aim 1 provides an important evaluation of the hypothesis that several response systems, as measured with behavioral, autonomic, and endocrine responses, will vary in parallel during repeated intermittent loud noise exposures, suggesting that only a few or perhaps a unique brain region undergoes the plastic changes associated with habituation. These results will guide the performance of most following studies, and provide some spatial and temporal guidance as the number of brain regions underlying this form of plasticity.
In Aim 2, functional manipulations of the auditory thalamus and auditory cortex will help determine the location, along the auditory system, where the auditory signal necessary and sufficient for habituation is derived from. Studies in Aim 3 are designed to ascertain the sympathetic premotor areas specifically controlling some of the measured autonomic responses, and help rule out the possibility that habituation to repeated loud noise is mediated by plasticity in these regions. Finally, the anatomical/functional studies of Aim 4 are designed to firmly establish the anatomical interface between activated auditory inputs and putative central integrative effector regions activated by loud noise. The hypothesis that functional inactivation of such central integrative effector region(s) will block habituation to repeated loud noise stress is also assessed.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Vicentic, Aleksandra
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University of Colorado at Boulder
Schools of Arts and Sciences
United States
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Nyhuis, Tara J; Masini, Cher V; Taufer, Kirsten L et al. (2016) Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats. Stress 19:248-59
Campeau, Serge (2016) Apparatus and General Methods for Exposing Rats to Audiogenic Stress. Bio Protoc 6:
Nyhuis, Tara J; Masini, Cher V; Day, Heidi E W et al. (2016) Evidence for the Integration of Stress-Related Signals by the Rostral Posterior Hypothalamic Nucleus in the Regulation of Acute and Repeated Stress-Evoked Hypothalamo-Pituitary-Adrenal Response in Rat. J Neurosci 36:795-805
Radley, Jason; Morilak, David; Viau, Victor et al. (2015) Chronic stress and brain plasticity: Mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders. Neurosci Biobehav Rev 58:79-91
Babb, Jessica A; Masini, Cher V; Day, Heidi E W et al. (2014) Habituation of hypothalamic-pituitary-adrenocortical axis hormones to repeated homotypic stress and subsequent heterotypic stressor exposure in male and female rats. Stress 17:224-34
Babb, Jessica A; Masini, Cher V; Day, Heidi E W et al. (2013) Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry. Stress 16:664-77
Babb, J A; Masini, C V; Day, H E W et al. (2013) Sex differences in activated corticotropin-releasing factor neurons within stress-related neurocircuitry and hypothalamic-pituitary-adrenocortical axis hormones following restraint in rats. Neuroscience 234:40-52
Masini, Cher V; Babb, Jessica A; Nyhuis, Tara J et al. (2012) Auditory cortex lesions do not disrupt habituation of HPA axis responses to repeated noise stress. Brain Res 1443:18-26
Newsom, R J; Osterlund, C; Masini, C V et al. (2012) Cannabinoid receptor type 1 antagonism significantly modulates basal and loud noise induced neural and hypothalamic-pituitary-adrenal axis responses in male Sprague-Dawley rats. Neuroscience 204:64-73
Masini, C V; Day, H E W; Gray, T et al. (2012) Evidence for a lack of phasic inhibitory properties of habituated stressors on HPA axis responses in rats. Physiol Behav 105:568-75

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