Monti / Pandi-Perumal / Jacobs Serotonin and Sleep: Molecular, Functional and Clinical Aspects

1. Auflage 2008
ISBN: 978-3-7643-8561-3
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 621 Seiten, eBook

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.

Zielgruppe

Research

Autoren/Hrsg.

Monti, Jaime M.

Pandi-Perumal, S. R.

Jacobs, Barry L.

Nutt, David J.

Inhaltsverzeichnis

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.

Leseproben

Brain serotonergic neuronal activity in behaving cats (p. 185-186)

Barry L. Jacobs and Casimir A. Fornal

Program in Neuroscience, Green Hall, Princeton University, Princeton, NJ 08540, USA

Abstract

A series of studies was conducted on the electrophysiological activity of brain serotonergic neurons in behaving cats. The studies explored a wide variety of behavioral and physiological conditions. In general, neuronal activity of both rostral (mesencephalic and pontine) and caudal (medullary) groups of serotonergic neurons was strongly related to spontaneous changes in behavioral state (highest in active waking and lowest during REM sleep).

Across a wide variety of behavioral and physiological conditions (including stressors), the activity of these neurons was relatively unperturbed. However, one condition, motor activity, strongly affected neuronal activity. A general relationship exists between level of tonic motor activity and serotonergic neuronal activity across all groups of serotonergic neurons. Superimposed upon this in some neurons is an additional relationship in which a further, often dramatic, activation is seen in association with repetitive, central motor program-mediated behaviors (e.g., feeding, licking, respiration, and locomotion). The exact nature of this relationship varies both with the serotonergic neuronal group (e.g., locomotor-related medullary neuronal activity versus grooming-related mesencephalic neuronal activity) and within a particular group (e.g., respiratory-related and feeding-related medullary neuronal activity). We hypothesize that the primary function of this increased serotonergic neuronal activity in association with tonic and repetitive motor activity is to facilitate behavioral output by coordinating autonomic and neuroendocrine function in association with the existing motor demand, and by concomitantly suppressing activity in most sensory information processing channels.

Introduction

For the past 30 years, the major goal of our laboratory’s research has been the elucidation of the behavioral/physiological role of the mammalian CNS serotonin (5-hydroxytryptamine, 5-HT) system. Does it have a specific role or roles, or is it a ubiquitous neurotransmitter, like GABA or glutamate, exerting effects on virtually all brain processes, and thus serving no specifiable behavioral or physiological function? Our feeling was that much of the research on brain serotonin was like the fable of the blind men and the elephant. Many people who studied the action of serotonin in a particular region of the CNS or in relation to a specific behavior or physiological process concluded, correctly, that this is what serotonin’s role was. For us, this was insufficient, it did not take the next step. Could all of these individual bits of data be integrated to form a whole, animated "elephant"? In other words, was there an overarching theory of CNS serotonin function that could account, at least in part, for the vast body of data on this topic?

The primary tool that we employed in our work was measuring the electrical activity of individual serotonergic neurons ("single-unit recordings") in unanesthetized, freely behaving domestic cats (F. catus). Our philosophy was to allow ourselves to be guided by the leads provided by observing the variations in neuronal activity that emerged under a diversity of behavioral and physiological conditions.

We are deeply indebted to a number of pioneering scientists whose research inspired, guided, and made our own work feasible. First, the value of the single- unit approach was dramatically and elegantly shown by the work of two laboratories. In the late 1950s and early 1960s, Hubel and Wiesel delineated the operating characteristics and function of visual system neurons in cats and monkeys. At the same time, Evarts showed the value of adapting this approach to behaving animals to study the function of various structures within the motor system of monkeys. Second, invertebrate neurophysiologists, led by Eric Kandel, showed the value of studying identifiable individual neurons in relation to various functional outputs. In our version of this, we studied "members" of identifiable groups of neurons (in vertebrates one cannot identify a "specific" serotonergic neuron). Third, in an extraordinary series of studies, in the late 1960s and early 1970s, George Aghajanian demonstrated that one could identify and reliably record the single-unit activity of brain serotonergic neurons in rats. Finally, the elegant research and brilliant theorizing of our friend and mentor, Michel Jouvet, regarding the role of serotonin in state control, was a direct inspiration and motivating force for our work.