Brain activity during rapid eye movement sleep (REM) resembles that of a state of hyperalertness, with electrophysiological features also found in alert waking (EEG activation, hippocampal theta and PGO wave activity). There is good evidence that the pinto-genicula-occipital (PGO) wave, a defining feature of REM, and its sound-elicited analog (PGO-epsilon) are neural indicators of alerting. Paradoxically, during REM, brain mechanisms of alerting are endogenously activated at the same time that largely unknown mechanisms prevent translation of that brain activity into behavioral arousal. The amygdala may have a role in modulating arousal and the generation of many of the features common to alert waking and REM. The central nucleus of the amygdala (CNA) projects prominently directly into brainstem regions important in the generation of REM and PGO waves. Thus, CNA provides a pathway by which the limbic system may influence alerting mechanisms and behavioral state; and it may be that this influence could be a significant factor in REM induction and maintenance. This project will examine CNA modulation of arousal and alerting in albino rats using standard indices (EEO, EMG, PGO, and PGO-epsilon waves) in both sleep and waking states by asking the following questions: l. Will electrical stimulation of CNA alter arousal state and spontaneous PGO wave activity across behavioral states? 2. Will the infusion of serotonergic (5-HT), adrenergic drugs or corticotropin releasing factor (CRF) into CNA alter arousal state and PGO wave generation? The 5-HT and NA systems are prominent in CNA, are important in REM and have demonstrated roles in PGO wave generation, and there is a major CRF input into brainstem PGO wave generator regions from CNA. This project will also examine CNA modulation of alerting mechanisms in waking using PGO-epsilon as a measure of activation PGO-epsilon responsiveness will be tested in the basic startle paradigm and in the fear-potentiated startle paradigm (the role of CNA in conditioned fear is demonstrated in the fear-potentiated startle paradigm) to answer the following questions: l. Will electrical stimulation of CNA increase the amplitude of the elicited PGO wave together with that of the acoustic startle reflex (ASR)? 2. Will PGO-epsilon be elicited in the fear-potentiated startle paradigm? and will lesions of CNA blocking fear- potentiated startle similarly block PGO-epsilon? 3. Will pharmacological manipulations of CNA, that increase or decrease ASR and/or fear- potentiated startle, similarly increase or decrease responsivity in brainstem mechanisms underlying PGO-epsilon? The involvement of the amygdala in modulating arousal state and alerting may have bearing on our understanding the dysfunctional emotionality and anxiety associated with many clinical conditions. These studies may also lead to a better understanding of disorders in which REM is altered For example, in narcolepsy, cataplectic attacks are abnormally triggered by emotional stimuli. REM may also be disturbed in posttraumatic stress disorder, which is characterized by hypervigilance to unfamiliar stimuli and stereotypical anxiety dreams.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
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Kitt, Cheryl A
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University of Pennsylvania
Veterinary Sciences
Schools of Veterinary Medicine
United States
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