The objective of this project is to further understanding of the nature of paradoxical sleep (PS), also known as rapid eye movement (REM) sleep. PS is a curious state in which the brain's activity resembles in many respects that observed during the orientation reaction to stimuli during wakefulness (W) without, of course, interactions with the external world. Cats prepared with chronic recording electrodes will be used to study the properties of a waveform (PGO wave) recorded in the lateral geniculate body originally thought to be solely a spontaneous event in PS, but which we have shown to be evokable by acoustic stimuli in both slow wave sleep and PS. We have also found that a wave form in W assumes characteristics similar to those of PGO waves when a cat is alerted. In W the response to stimuli habituates, but preliminary evidence indicates that PGO waves may not. Lack of habituation at the brainstem level may be a feature of PS, with arousal into W prevented by some mechanism at a higher level of the nervous system. Because we can eliminate the usual paralysis of PS by means of pontine lesions and thereby observe elaborate behavior in that state, we may also have a behavioral measure of responses to stimuli in PS as well as W. At a superficial level PGO waves bear a resemblance to the acoustic startle reflex in their response to pharmacologic manipulation with serotonergic agents. The wealth of more sophisticated pharmacologic data obtained in studies of the startle reflex will be used to compare properties of PGO waves and startle in an effort to determine how each is related to the basic process of alerting of the nervous system. Traumatic stress disorder, occasioned by emotionally powerful experiences, provide an especially promising area for clinical application of basic research in sleep and alerting. Stress disorder, such as the so-called """"""""war-neurosis"""""""" (post-traumatic stress syndrome), commonly includes both prominent sleep disturbances like nightmares and extreme ease of startle. These illnesses are often refractory to behavioral and pharmacological interventions. Our hope is that clarifying the behavioral and pharmacological properties of alerting as a """"""""paradoxical"""""""" phenomenon of one phase of sleep will contribute to the rational treatment of these costly and very painful conditions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Method to Extend Research in Time (MERIT) Award (R37)
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Neurosciences Research Review Committee (BPN)
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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