CNS Neurotransmitters and Neuromodulators

Acetylcholine

Trevor W. Stone

• Editorial: CRC Press
• Año: 2020
• ISBN:
  9781000142112
• Edición: 1
• Categoría: Sciences biologiques
• Categoría: Biologie

The series CNS Neurotransmitters and Neuromodulators is destined to be the definitive reference work on the physiology and pharmacology of the central nervous system. Written by an outstanding group of international authors, chapters cover a wide range of interdisciplinary aspects of the subject.
This first volume includes an in-depth examination of acetylcholine, ranging from the localization of synthetic enzymes through electrophysiology, pharmacology, and molecular biology to behavioral importance in learning and memory. This indispensable and comprehensive reference keeps you abreast of new developments in several areas of neuroscience.

Chapter 1

The Localization of Cholinergic Neurons and Markers in the CNS

Ricardo Martínez-Murillo and José Rodrigo

CONTENTS

I.	Introduction
II.	Considerations on the Methodologies for Visualizing Cholinergic Structures A. AChE Histochemistry B. AChE Pharmacohistochemistry C. Immunocytochemistry of ACh D. Immunocytochemistry of ChAT E. In Situ Hybridization of ChAT mRNA F. Cytochemical Markers of Cholinergic Neurons Other Than ChAT
III.	Organization and Major Projections of Cholinergic Neurons of the Brain A. Cholinergic Neurons in the Telencephalon 1. Projection Neurons 2. Local Circuit Neurons B. Cholinergic Neurons in the Diencephalon C. Cholinergic Neurons in the Mesencephalon, Pons, and Medulla 1. Midbrain and Pons 2. Spinal Cord D. Cholinergic Neurons in the Cerebellum
IV.	Cytological Characteristics of Central Cholinergic Neurons A. Light Microscopy B. Electron Microscopy C. Cholinergic Terminals
V.	Transmitter-Specific Afferents to Central Cholinergic Neurons
Acknowledgments
References

Summary: Convincing evidence that acetylcholine (ACh) is a neurotransmitter contained in a variety of central nervous system pathways has been available for some years (see Kasa¹ and Wainer et al., ² for a broad overview), ACh occupying a historically senior position among neurotransmitter candidates. ACh was first described by Loewi (1921) as “Vagustoff’ in the frog heart. However, only in the last few years has the field of neuroanatomy allowed, after a growth in research technology, the unequivocal visualization of cholinergic structures. Convincing conclusions on the cholinergic neuroanatomy of the central nervous system were gained by using histochemical tools, including AChE pharmacohistochemistry, immunocytochemistry, and in situ hybridization procedures. In addition, the anatomic technology has benefited from an interdisciplinary strategy, and it is now possible to combine behavioral or physiological experiments with tracing and/or lesioning of neuronal pathways and with histochemical characterization of the pathways involved. These methodologies will be discussed briefly below.

I. INTRODUCTION

The cholinergic system in the central nervous system (CNS) consists of several neuronal components which are localized throughout the rostrocaudal extent of the brain and spinal cord. Since there was not any available histochemical procedure for direct visualization of ACh, the demonstration of the ACh inactivating enzyme — acetyl cholinesterase (AChE) — was first employed, in combination with lesion- induced procedures, for an earliest anatomic clarification of the CNS cholinergic system in a classical series of experiments.^{3, 4, 5} These studies are of exceptional relevance in the history of chemical neuroanatomy in that they were among the first to be developed for the general purpose of identifying chemically distinctive classes of cells. These experiments^{3, 4, 5} were based on the hypothesis that cholinergic neurons contain detectable levels of AChE in the cell body and processes. Shute and Lewis’s consequential conclusion was the identification of two major cholinergic afferents to the forebrain, termed dorsal and ventral tegmental pathways, arising in the pontomesencephalic region. The ventral tegmental AChE pathway described by Shute and Lewis represents the dopamine-containing projection system that originates in the substantia nigra and ventral tegmental area project to the striatum, nucleus accumbens, olfactory tubercle, and frontal cortex.^{6, 7, 8} It is well known that the AChE ventral tegmental pathway consistently lacks the ACh synthesizing enzyme, choline acetyltransferase (ChAT), considered as an unquestionable marker for cholinergic structures.⁹ Therefore, although the histochemical description concerning the ventral tegmental AChE-containing pathway to the forebrain is precise, the conclusion concerning the cholinergic nature of this projection was erroneous. Nevertheless, the cholinergic nature of some other pathways described as containing heavy AChE staining by Shute and Lewis⁴ and Lewis and Shute,⁵ has been subsequently confirmed, for example, the septo-hippocampal pathway¹⁰ and the dorsal tegmental projection to the forebrain.¹¹

In general, the use of AChE histochemistry for examining cholinergic neurons has resulted in conflicting results. In the cerebral cortex, for example, some investigators have not found stained cell bodies following AChE histochemistry, concluding that the cortical mantle does not contain intrinsic cholinergic perikarya.^{12, 13, 14, 15} Others, however, have reported strong staining in a population of AChE- positive cortical cells.^16,17 However, these cells were found to be non-cholinergic.¹⁸

Extensive basic and clinical literature has linked ACh with memory function. These studies give information on how the central cholinergic system is involved in functions representing the highest levels of integration, including cortical arousal, sleep-wakefulness cycles, selective attention, learning, memory, and discrimination processes (see Arendt et al.,¹⁹ Dekker et al.,²⁰ and Jones,²¹ for a broad overview), as well as in cortical sensory processing.²² These facts inspired an effort to better define the role that the central cholinergic system plays in human cognitive processes. To date, however, the precise neuronal circuits involved and the physiological basis of the control of memory are still relatively poorly understood. Impairment of central cholinergic function has been associated with normal aging processes and in a number of neurological diseases associated with amnesia or dementia including Alzheimer’s, Parkinson’s and Korsakoff s diseases; dementia of the Alzheimer’s type; postalcoholic dementia; and others.^{19,23, 24, 25} Cholinergic neurons have also been implicated in delirium in demented patients²⁶ and schizophrenia.²⁷ A decay in neurochemical markers linked to cholinergic function (ChAT, AChE, and muscarinic binding sites) in the cerebral cortex was found to be correlated with the grade of impairment of cognitive function and with the extent of damage to the cholinergic cortical projection system in the basal forebrain.^{25,28, 29, 30} It is, however, unclear as to whether these cholinergic changes are the cause or result of the disease.^{31, 32, 33} Because of central cholinergic vulnerability in neurological disorders underlying cognitive deterioration, major research to establish the role of cholinergic neurons in these processes was attempted with the aim of providing potential therapeutic trials in patients exhibiting cognitive deficits.

Approximately 70% of the cholinergic innervation of the neocortex, hippocampus, amygdala, and olfactory bulb arises from neurons in the basal forebrain,³⁴ through which cholinergic transmission may modulate the activity of these telencephalic areas. It has been reported that 30% of neocortical neurons is cholinoceptive, and for most of these application of ACh increases the rate of firing.³⁵ In addition, it seems that ACh released from cholinergic fibers of the basalocortical pathway influences the morphological development of the cerebral cortex³⁶ and exerts a facilitatory, permissive role, in processes of synaptic plasticity during a critical postnatal period^37,38 and during adulthood.³⁹ While there is ample evidence for a role of ACh in the control of cerebral blood flow, it appears that the cortical cholinergic afferents originating in the basal forebrain are not involved in such an event.^40,41 It is presumed that ACh released from intrinsic cortical cholinergic cells may mediate the cerebrovascular action.

The proven implication of central cholinergic transmission in higher brain processes, as well as in neocortical development and plasticity, has made understanding of the morphology and distribution of cholinergic neurons the subject of considerable attention and continued reinvestigation and reappraisal. To elucidate the structural organization, cytochemistry, and functional connections of the central cholinergic system in different species will provide a new viewpoint relevant to its functional significance in normal and diseased brains, particularly the pathophysiological implications of its degeneration in Alzheimer’s disease and the dementia acco...

Índice

• Cover
• Title Page
• Copyright Page
• Preface
• The Editor
• Contributors
• Table of Contents
• Chapter 1 The Localization of Cholinergic Neurons and Markers in the CNS
• Chapter 2 Subtypes of Neuronal Muscarinic Receptors: Pharmacological Criteria
• Chapter 3 Subtypes of Muscarinic Receptors: Receptor Structure and Molecular Biology
• Chapter 4 Distribution of Muscarinic Acetylcholine Receptors in the CNS
• Chapter 5 Distribution of Nicotinic Receptors in the CNS
• Chapter 6 Function of Nicotinic Receptors in the CNS
• Chapter 7 Electrophysiological Effects of Acetylcholine on Central Neurons (Whole Cells and Interactions)
• Chapter 8 Acetylcholine-Operated Ionic Conductances in Central Neurons
• Chapter 9 Neurochemical Transduction Processes Associated with Neuronal Muscarinic Receptors
• Chapter 10 Compartmentalization and Release from Neurons in the CNS
• Chapter 11 Muscarinic Acetylcholine Receptors and Long-Term Potentiation of Synaptic Transmission
• Chapter 12 Nicotinic Receptors and Information Processing
• Chapter 13 Cholinergic Neurons and Memory: An Historical Perspective and Overview of Current Research
• Chapter 14 Nerve Growth Factor: Influence on Cholinergic Neurons in the CNS
• Index