This project seeks further understanding of the mechanisms underlying the generation and maintenance of one phase of sleep, REM sleep. REM normally follows the other stages of sleep, collectively known as non-REM (NREM). Its differentiating features are a total paralysis of skeletal muscles with superimposed phasic muscle twitches, electroencephalographic activity resembling wakefulness rather than NREM, and profound depression of the brain mechanisms regulating homeostasis, i.e., those controlling such vital features of life as temperature, cardiovascular activity and respiration. Further, as we demonstrated 20 years ago, the brain in REM functions much like the brain during orienting in wakefulness. The project's focus will be study of the activity of nerve cells in the amygdala of the forebrain of rats and their interactions with those in the pons of the hindbrain that have long been studied and heavily implicated in the control of REM. The investigator is stimulated by the facts that the amygdala and pons are tightly interconnected and that the amygdala is a key structure investing environmental stimuli with emotional significance. Thus, a change in sensitivity of structures like the amygdala to arousing stimuli must precede entrance into REM. Indeed, in narcoleptics the shift to REM is so poorly modulated that sufferers enter REM directly from wakefulness when confronted by such stimuli. The investigator shall record single-neuronal activity in three amygdalar nuclei, the central (CNA), basolateral (BLA) and lateral (LA), across sleep-wake states. The investigator shall determine how stimulation and suppression of key pontine neurons of different transmitter types, serotonergic, noradrenergic and cholinergic, affect spontaneously active amygdalar neurons and those responding to novel or significant auditory stimuli. These experiments address basic mechanisms likely to be altered in narcolepsy and PTSD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
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University of Pennsylvania
Veterinary Sciences
Schools of Veterinary Medicine
United States
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Sanford, L D; Silvestri, A J; Ross, R J et al. (2001) Influence of fear conditioning on elicited ponto-geniculo-occipital waves and rapid eye movement sleep. Arch Ital Biol 139:169-83
Sanford, L D; Hunt, W K; Ross, R J et al. (1998) Microinjections into the pedunculopontine tegmentum: effects of the GABAA antagonist, bicuculline, on sleep, PGO waves and behavior. Arch Ital Biol 136:205-14
Sanford, L D; Tejani-Butt, S M; Ross, R J et al. (1995) Amygdaloid control of alerting and behavioral arousal in rats: involvement of serotonergic mechanisms. Arch Ital Biol 134:81-99
Ross, R J; Ball, W A; Gresch, P J et al. (1990) REM sleep suppression by monoamine reuptake blockade: development of tolerance with repeated drug administration. Biol Psychiatry 28:231-9
Ross, R J; Ball, W A; Levitt, D R et al. (1990) Effects of monoamine reuptake blockade on ponto-geniculo-occipital wave activity. Neuropharmacology 29:965-8
Ball, W A; Morrison, A R; Ross, R J (1989) The effects of tones on PGO waves in slow wave sleep and paradoxical sleep. Exp Neurol 104:251-6