Serotonin and Sleep: Molecular, Functional and Clinical Aspects

Foreword Barry Jacobs once memorably commented that the problem in understanding the role of serotonin in the brain was that it was implicated in virtually eve- thing but responsible for nothing [1]. Serotonin (5-HT) is defnitely implicated in the regulation of sleep but what does it do? Once seen as a sleep-promoting molecule, Jacob’s own work, lucidly described in this volume, radically changed our view. In fact, serotonin neurons are most active during waking; their - tivity diminishes with sleep onset and disappears during rapid eye movement (REM) sleep. Serotonin, therefore, is intimately linked to the sleep-wake cycle, but what is its role, what mechanisms are involved and what are the impli- tions for sleep medicine and psychiatry? Making progress with these diffcult questions requires a “translational” approach, which is a research paradigm where both laboratory and clinical neuroscience inform and guide each other with the ultimate aim of improving understanding and treatment of medical conditions. This volume is a superb example of translational research, where leading basic and clinical scientists - tegrate molecular, neuropharmacological and systems approaches to illuminate the reciprocal interactions of serotonin neurons and the mechanisms involved in sleep and circadian regulation. Serotonin is an ancient chemical mediator preserved through at least 500 m- lion years of evolution. In invertebrate animals such as mollusks and leeches, 5-HT cells are distributed throughout the nervous system among the various ganglia.

Foreword Barry Jacobs once memorably commented that the problem in understanding the role of serotonin in the brain was that it was implicated in virtually eve- thing but responsible for nothing [1]. Serotonin (5-HT) is defnitely implicated in the regulation of sleep but what does it do? Once seen as a sleep-promoting molecule, Jacob's own work, lucidly described in this volume, radically changed our view. In fact, serotonin neurons are most active during waking; their - tivity diminishes with sleep onset and disappears during rapid eye movement (REM) sleep. Serotonin, therefore, is intimately linked to the sleep-wake cycle, but what is its role, what mechanisms are involved and what are the impli- tions for sleep medicine and psychiatry? Making progress with these diffcult questions requires a "e;translational"e; approach, which is a research paradigm where both laboratory and clinical neuroscience inform and guide each other with the ultimate aim of improving understanding and treatment of medical conditions. This volume is a superb example of translational research, where leading basic and clinical scientists - tegrate molecular, neuropharmacological and systems approaches to illuminate the reciprocal interactions of serotonin neurons and the mechanisms involved in sleep and circadian regulation. Serotonin is an ancient chemical mediator preserved through at least 500 m- lion years of evolution. In invertebrate animals such as mollusks and leeches, 5-HT cells are distributed throughout the nervous system among the various ganglia.

Foreword Barry Jacobs once memorably commented that the problem in understanding the role of serotonin in the brain was that it was implicated in virtually eve- thing but responsible for nothing [1]. Serotonin (5-HT) is defnitely implicated in the regulation of sleep but what does it do? Once seen as a sleep-promoting molecule, Jacob’s own work, lucidly described in this volume, radically changed our view. In fact, serotonin neurons are most active during waking; their - tivity diminishes with sleep onset and disappears during rapid eye movement (REM) sleep. Serotonin, therefore, is intimately linked to the sleep-wake cycle, but what is its role, what mechanisms are involved and what are the impli- tions for sleep medicine and psychiatry? Making progress with these diffcult questions requires a “translational” approach, which is a research paradigm where both laboratory and clinical neuroscience inform and guide each other with the ultimate aim of improving understanding and treatment of medical conditions. This volume is a superb example of translational research, where leading basic and clinical scientists - tegrate molecular, neuropharmacological and systems approaches to illuminate the reciprocal interactions of serotonin neurons and the mechanisms involved in sleep and circadian regulation. Serotonin is an ancient chemical mediator preserved through at least 500 m- lion years of evolution. In invertebrate animals such as mollusks and leeches, 5-HT cells are distributed throughout the nervous system among the various ganglia.

Evolution of concepts.- Changing concepts on the role of serotonin in the regulation of sleep and waking.- The dorsal raphe nucleus and median raphe nucleus: organization and projections.- Topographic organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus.- Efferent and afferent connections of the dorsal and median raphe nuclei in the rat.- Reciprocal connections between the suprachiasmatic nucleus and the midbrain raphe nuclei: A putative role in the circadian control of behavioral states.- Serotonin receptors.- Localization of 5-HT receptors in the mammalian cortex.- Molecular biology of 5-HT receptors.- Electrophysiology of serotonergic neurons and the regulation of serotonin release.- Brain serotonergic neuronal activity in behaving cats.- Electrophysiological studies on serotonergic neurons and sleep.- Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons.- Regulation of serotonin release by inhibitory and excitatory amino acids.- Neurophysiological aspects of the regulation of serotonin neurons by the orexinergic system.- Serotonin receptors and the regulation of behavioural state.- Serotonin and dreaming.- Involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking.- Mechanisms involved in the inhibition of REM sleep by serotonin.- Effect of 5-HT2A/2B/2C receptor agonists and antagonists on sleep and waking in laboratory animals and humans.- Effect of the selective activation of serotonin 5-HT3 receptors on sleep and waking.- 5-HT7 receptor modulation of sleep patterns.- Sleep and waking in mutant mice that do not express various proteins involved in serotonergic neurotransmission such as the serotonergic transporter, monoamine oxidase A, and 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT7 receptors.- Circadian control by serotonin and melatonin receptors: Clinical relevance.- Serotonergic mechanisms contributing to arousal and alerting.- Relevance of serotonin to clinical disorders and drug actions.- Contribution of chemosensitive serotonergic neurons to interactions between the sleep-wake cycle and respiratory control.- Obstructive sleep apnea: The potential for serotonergic pharmacotherapies.- The effects of antidepressant drugs and 5-HT1A agonists on human sleep.- The effect of typical and atypical antipsychotic drugs on sleep of schizophrenic patients.