Segment 3

Historical Overview: Brainstem & Forebrain

Neurobiology of Sleep and Wakefulness

Learning Points & Defining Behavioral States Historical Overview: Brainstem & Forebrain Wakefulness and REM Sleep: Monoamines,

Acetylcholine & GABA, Hypocretin/Orexin NREM Sleep: GABA, Adenosine Summary

Brainstem Control of REM Sleep and Wakefulness

Pons Midbrain

Medulla

Deafferentation Hypothesis: Sleep is a Passive Process

Bremer, Bull Acad Royale Medicine Belgique 4: 6886, 1937

Moruzzi and Magoun, 1949Electroencephalog Clin Neurophysiol 1:455-473

Ascending Reticular Activating System (ARAS)

Brain stem reticular formation and activation of the EEG

First Recordings of Eye Movements During Sleep

Regularly occurring periods of eye motility and concomitant phenomena, during sleep

Aserinsky and Kleitman Science 118:273-274, 1953

200 100

V

Conjugate Rapid Eye Movements

0 5 15 20 Time (sec)

Cyclic Variations in EEG During Sleep and Their Relations to Eye Movements,

Body Motility and Dreaming

William C. Dementand Nathanial Kleitman

Electroencephalog Clin Neurophysiol9:673-680, 1957

EEG Activation During Sleep in Animals

Dement, Electroencephalog Clin Neurophysiol 10:291-296, 1958

modified from Jouvet, Arch Ital Biol 100:125-206, 1962

REM Sleep Generating Neurons are Localized to the Pons

A B C

Putative cholinergic neurons in the brainstem were identified and localized (Shute and Lewis, Nature 199:1160-1164, 1963)

Monoamine-containing neurons in the brain stem were histologically identified and mapped (Dahlstrm and Fuxe, Acta Physiol Scand 62 (Suppl. 232):1-55, 1964)

Anatomical Basis of the ARAS

Cholinergic Components of the ARAS

modified from Cooper et al., 1991 Biochemical Basis of Neuropharmacology, Oxford, p. 208

Human ARAS PET image shows activation of mesopontine tegmentum when a subject performs an attention-demanding task

Kinomura et al.,Science 271:417-564, 1996

Braun et al., Brain 120:1173-1197, 1997

NREM

REM

WAKE

REM Sleep is an Active Brain State that is Actively Generated

Lydic et al., J Comp Neurol 304:517-529,1991

REM Sleep

Wakefulness

Forebrain Control of NREM Sleep and Wakefulness

Hypothalamus

Basal Forebrain

Basal Forebrain and Hypothalamus Regulate Sleep and Wakefulness

Post mortem examination of brains from encephalitis lethargica patients revealed different effects on sleep depending on lesion site (von Economo, Journal of Nervous and Mental Disease 71:249-259, 1930)

Patients with insomnia had lesions of the preoptic area and anterior hypothalamus (von Economo, Journal of Nervous and Mental Disease 71:249-259, 1930)

X

Basal Forebrain and Hypothalamus Regulate Sleep and Wakefulness

Patients with hypersomnolence had lesions of the posterior hypothalamus (von Economo, Journal of Nervous and Mental Disease 71:249-259, 1930)

Basal Forebrain and Hypothalamus Regulate Sleep and Wakefulness

Preoptic area/anterior hypothalamus functions as a sleep center, and posterior hypothalamus functions as a wakefulness center (von Economo, Ergebnisse der Physiologie 28:312-339, 1929; J Nerv Ment Dis 71:249-259, 1930)

Basal Forebrain and Hypothalamus Regulate Sleep and Wakefulness

Experimental lesions of the anterior hypothalamus cause insomnia (McGinty and Sterman, 1968; Nauta, 1946; Sallanon et al., 1989)

Experimental lesions of the posterior hypothalamus cause hypersomnolence (Ranson, 1939; Nauta, 1946; McGinty, 1969; Sweet and Hobson, 1968)

Electrical stimulation of the preoptic area-anterior hypothalamus causes sleep (Sterman and Clemente, 1962)

Hypothalamic Regulation of Sleep and Wakefulness