The Enteric Nervous System II

Preface
Contents
1: Contribution of the Enteric Nervous System to Autoimmune Diseases and Irritable Bowel Syndrome
1.1 Enteric Nervous System and Autoimmune Disease
1.2 Enteric Nervous System and Irritable Bowel Syndrome
References
2: Clinical and Pathological Features of Severe Gut Dysmotility
2.1 Introduction
2.2 Genetics of CIPO
2.2.1 RAD21
2.2.2 LIG3
2.3 Smooth Muscle Actin–Related Diseases: Visceral Myopathy Driven by ACTG2 Mutations
2.4 Conclusion and Future Perspectives
References
3: Luminal Chemoreceptors and Intrinsic Nerves: Key Modulators of Digestive Motor Function
3.1 Introduction
3.2 Spectrum of Duodenal Chemosensing
3.3 Effects of Truncal Vagotomy on Duodenal Chemoreceptor Control of Gastric Emptying
3.4 Chemosensor Control of Proximal Gastric Motor Function
3.5 Duodenal Chemoreceptor Control of Antro-Pyloric Motor Function
3.5.1 Measurement of Antral and Pyloric Motor Functions
3.5.2 Chemoreceptor Control of Antral and Pyloric Motor Functions in Humans
3.5.3 Studies in Pigs and Dogs of Pathways via Which Duodenal Chemoreceptors Alter Antral and Pyloric Motor Function
3.6 Synthesis: Paths of Duodenal Chemoreceptor Control of Antral and Pyloric Motor Function During Normal Nutrient Processing
3.7 Duodenal Chemoreceptors and the Duodenal Brake Mechanism
3.7.1 Fluoroscopic Demonstration of the Duodenal Brake
3.7.2 Manometric Definition of the Duodenal Brake
3.8 Synthesis: Interpretation of Duodeno-Jejunal Complex Activity
3.8.1 Spatial Correlation of DJC Activity
3.8.2 The Mechanical Outcome of DJC Activity
3.8.3 Entry of Chyme into the Duodenum Stimulates DJC Activity
3.8.4 Physiological Significance of DJC Activity
3.8.5 Pathways of Stimulation of DJC Activity
3.9 Potential Clinical Significance of the Duodenal Brake
References
4: Nitrergic and Purinergic Nerves in the Small Intestinal Myenteric Plexus and Circular Muscle of Mice and Guinea Pigs
4.1 Introduction
4.2 Materials and Methods
4.2.1 Animals
4.2.2 Tissue Preparation
4.2.3 Fluorescence Microscopy
4.3 Results
4.3.1 Nitric Oxide Synthase (NOS)
4.3.2 Choline Acetyltransferase (ChAT)
4.3.3 Calbindin (CalB)
4.3.4 Calretinin (CalR)
4.4 Discussion
4.4.1 VNUT-ir and NOS-ir
4.4.2 VNUT-ir and ChAT-ir
4.4.3 VNUT-ir and CalB-ir
4.4.4 VNUT-ir and CalR-ir
4.4.5 Summary and conclusions
References
5: Mechanosensitive Enteric Neurons (MEN) at Work
5.1 Enteric Nervous System and Mechanosensitive Enteric Neurons
5.2 Methods Used to Identify MEN
5.3 Nature of the Mechanosensitive Stimuli Activating MEN: Sensitivity to Compression, Tension and Shear Stress
5.4 Properties of Isolated Myenteric MEN
5.5 Regional- and Species-Specific Differences in the Properties of MEN
5.6 Deformation Rate
5.7 Myenteric and Submucosal MEN
5.8 MEN Neurochemical Phenotype
5.9 Pharmacology of MEN
5.10 Multifunctionality
5.11 Outlook
References
6: New Concepts of the Interplay Between the Gut Microbiota and the Enteric Nervous System in the Control of Motility
6.1 Introduction
6.2 Microbial Regulation of Enteric Neurons and Enteric Glia
6.3 Gut Bacteria Interact with Toll-Like Receptors and Enterochromaffin Cells to Regulate the Integrity of the ENS and Control GI Motility
6.4 Toll-Like Receptors as Regulators of Intestinal Motility
6.4.1 Deletion of TLR2 and TLR4 Impacts the Integrity of the ENS and Alters Motility
6.4.2 TLRs Are Modulated by Gut Microbiota Affecting Gut Transit, Neurogenesis, and Glial-Derived Neurotrophic Factor (GDNF)
6.5 Microbial Regulation of Serotonin in Enterochromaffin Cells
6.5.1 Potential Mechanisms for Microbiota Modulation of 5-HT Metabolism and GI Motility
6.6 Conclusions and Future Directions
References
7: Optical Approaches to Understanding Enteric Circuits Along the Radial Axis
7.1 Introduction
7.2 The Development of the Intrinsic Sensory Innervation of Mucosa
7.3 Sensing Microbial Metabolites
7.4 Coordinating Activity in the Myenteric and Submucosal Plexus
7.5 Future Perspectives
References
8: Serotonergic Paracrine Targets in the Intestinal Mucosa
8.1 Overview
8.2 Enterochromaffin Cells
8.3 Enterochromaffin Cells
8.4 Enteric Mast Cells
8.5 Paracrine Linkage of Enterochromaffin Cells to Mast Cells
8.6 Paracrine Linkage of Enteric Mast Cells to Spinal Afferents
8.7 Spinal Afferents Degranulate Enteric Mast Cells
References
9: Enteric Control of the Sympathetic Nervous System
9.1 Central Sympathetic Circuits
9.2 Peripheral Sympathetic Circuits
9.3 Enteric Viscerofugal Neurons
9.4 The ENS-SNS Interface in Prevertebral Ganglia
9.5 Viscerofugal Neurons as Enteric Mechanoreceptors
9.6 Viscerofugal Neurons as Interneurons
9.7 Viscerofugal Neurons and Neurogenic Motor Behaviors
9.8 Enteric Control of the Sympathetic Nervous System
9.8.1 Effector Function of ENS-Driven Sympathetic Firing
References
10: Embryonic Development of Motility: Lessons from the Chicken
10.1 The First Digestive Movements Are Just Calcium Waves in a Tube of Circular Smooth Muscle
10.2 Early Smooth Muscle Contractility Is Essential for Anisotropic Longitudinal Growth of the Gut
10.3 The Interstitial Cell of Cajal Transition
10.4 Early Enteric Nervous System Activity
10.5 Outlook
References
11: Activation of ENS Circuits in Mouse Colon: Coordination in the Mouse Colonic Motor Complex as a Robust, Distributed Control System
11.1 Introduction
11.2 History of Evoked Colonic Migrating Motor Complexes
11.3 Coordination in the Colonic Migrating Motor Complex
11.3.1 Subthreshold Rapid Oscillations in the Smooth Muscle
11.3.2 Myenteric Potential Oscillations and the Role of Interstitial Cells
11.3.3 Enteric Neuron Synchronization During Motor Complex Initiation
11.3.4 Coordination in a Robust, Distributed Control System
11.4 Perturbing the Control System and the Colonic Migrating Motor Complex
11.4.1 Initiating a Colonic Migrating Motor Complex by Nonphysiological Stimulation
11.4.2 Disrupting Coordination in the Colonic Migrating Motor Complex
11.5 Concluding Remarks
References
12: Colonic Response to Physiological, Chemical, Electrical and Mechanical Stimuli; What Can Be Used to Define Normal Motility?
12.1 Protocols and Catheter Types
12.2 Colonic Motor Patterns
12.3 Colonic Response to a Meal
12.4 Colonic Response to Chemical Stimulation
12.5 Colonic Response to Distension
12.6 Colonic Response to Gas Insufflation
12.7 Summary, Current Limitations and Future Directions
References
13: New Insights on Extrinsic Innervation of the Enteric Nervous System and Non-neuronal Cell Types That Influence Colon Function
13.1 Introduction
13.2 Distinct ENS Organization and Function in Proximal and Distal Colon
13.3 Lumbosacral (LS) Pathway
13.4 Thoracolumbar (TL) Pathway
13.5 Vagal Pathway
13.6 Summary
References
14: The Emerging Role of the Gut–Brain–Microbiota Axis in Neurodevelopmental Disorders
14.1 Introduction
14.2 Gastrointestinal Symptoms in Autism
14.3 Genetic Contributions to Autism
14.4 Microbial Dysbiosis
14.5 Preclinical Studies
14.6 Gastrointestinal Dysfunction in Patients and Mice Expressing the Autism-Associated R451C Mutation in Neuroligin-3
14.7 Neuroinflammation in Autism
14.7.1 Altered Caecal Neuroimmune Interactions in Mouse Models of Autism
14.8 The Gastrointestinal Mucus Environment and Implications for Neurodevelopmental Disorders
14.9 Region-Specific Motility Patterns
14.10 Examining Microbial Changes in Neurodevelopmental Disorders
14.11 Conclusion
References
15: Interaction of the Microbiota and the Enteric Nervous System During Development
15.1 The ENS and Microbiota Develop Concurrently
15.2 Role of Microbiota on the Developing ENS
15.3 Implications of Antibiotic Exposure During Critical Developmental Windows
15.4 Conclusions and Future Directions
References
16: Comparative and Evolutionary Aspects of the Digestive System and Its Enteric Nervous System Control
16.1 Nutritional Strategies of Simple Life Forms
16.2 Design Features of the Vertebrate Digestive System
16.2.1 Nutrient Exchange
16.3 Comparisons of Digestive Strategies in Mammals
16.3.1 Ruminant Foregut Fermenters
16.3.2 Autoenzyme Digesters: Carnivores, Omnivores and Cucinivores
16.3.3 Cucinivores
16.3.4 Extremes of Diversity
16.4 The Enteric Nervous System
16.5 Essential Nature of the ENS
16.5.1 Evolution of the Enteric Nervous System
16.6 Reciprocal and Convergent Connections of the ENS and CNS
16.7 Did an Ancient Nervous System Lead to the Enteric Nervous System in Cnidaria and the ENS and CNS in Vertebrates, Including Human?
16.8 Conclusions
References
17: Enteric Glia and Enteric Neurons, Associated
17.1 Cytology of Glia
17.2 Glial Populations
17.3 Relative Extent of Glia
17.4 Glial Chondrioma
17.5 Research Limitations
17.6 Ganglionic Dense Packing
17.7 Dynamic Form of Ganglia
17.8 Life Times
References
18: Circadian Control of Gastrointestinal Motility
18.1 Clock Genes
18.2 Circadian Cycle and the Gut
18.2.1 Nutrient Absorption and Metabolism
18.2.2 Regulation of Intestinal Epithelial Cell Proliferation and Cancer
18.2.3 Immune Function and Influence of the Microbiota
18.3 Gastrointestinal Motility and the Enteric Nervous System
18.3.1 Circadian Cycle and Gastrointestinal Motility
18.3.2 Molecular Mechanisms Underlying Circadian Control of Gut Motility
18.4 Conclusions
Bibliography
References
19: Generation of Gut Motor Patterns Through Interactions Between Interstitial Cells of Cajal and the Intrinsic and Extrinsic Autonomic Nervous Systems
19.1 ICC as Intermediary of Sensory and Motor Activities of the Vagus
19.2 The Migrating Motor Complex (MMC)
19.3 Duodenal Propulsive Activity
19.4 The Minute Rhythm Contraction Pattern in the Human Small Intestine
19.5 The Segmentation Motor Pattern as Described by Cannon
19.6 The High-Amplitude Propagating Pressure Wave (HAPW) in the Human Colon
References
20: Refining Enteric Neural Circuitry by Quantitative Morphology and Function in Mice
20.1 Introduction
20.2 Quantitative Morphology
20.3 Functional Connectivity
20.4 Conclusion
References
21: Molecular Targets to Alleviate Enteric Neuropathy and Gastrointestinal Dysfunction
References
22: Ca2+ Signaling Is the Basis for Pacemaker Activity and Neurotransduction in Interstitial Cells of the GI Tract
22.1 Introduction
22.2 Basal Ca2+ Transients in Interstitial Cells
22.3 Neurotransduction by Interstitial Cells
22.4 Pacemaker Activity in Interstitial Cells
22.5 Conclusions
References
23: Identifying Types of Neurons in the Human Colonic Enteric Nervous System
23.1 Classifying Neurons
23.1.1 Goals for Classification
23.2 The Opportunity to Study Human Enteric Nervous System
23.2.1 Technical Issues with Use of Human Tissue
23.3 Classification of Enteric Neurons
23.4 Chemical Coding
23.5 Limits of Chemical Coding
23.6 A New Approach to Chemical Coding
23.7 Discussion
References
24: Neurons, Macrophages, and Glia: The Role of Intercellular Communication in the Enteric Nervous System
24.1 Introduction
24.2 The Role of EGCs in ENS Communication
24.3 Communication Between Neighboring EGCs
24.4 The Role of mMacs in ENS Communication
24.5 How Do mMac Interactions with Enteric Neurons Relate to Changes to Gastrointestinal Function?
24.6 Evidence for EGC and mMac Interactions in the Gut Wall
24.7 Conclusion
References
25: Mas-Related G Protein-Coupled Receptors (Mrgprs) as Mediators of Gut Neuro-Immune Signaling
25.1 The Family of Mas-Related G Protein-Coupled Receptors
25.2 Mrgprs in the Skin Sensory Innervation
25.2.1 Mrgpra3 and MRGPRX1
25.2.2 Mrgpra1/MRGPRX4
25.2.3 Mrgprb4
25.2.4 Mrgprc11 and MRGPRX1
25.2.5 Mrgprd
25.3 Mrgprs in Skin Immune Cells
25.4 Mrgprs Expression in the Gastrointestinal (GI) Tract
25.4.1 Mrgprs in the Enteric Nervous System
25.4.2 Mrgprs in the Gut Spinal Afferent Innervation
25.4.2.1 Mrgpra3/c11 and Its Human Counterpart MRGPRX1
25.4.2.2 Mrgprd
25.4.3 Mrgprs: Novel Targets in Chronic Abdominal Pain Disorders?
25.4.4 Mrgprs in Gut Mast Cells
25.5 Conclusion
References
26: Analysis of Intestinal Movements with Spatiotemporal Maps: Beyond Anatomy and Physiology
26.1 Introduction
26.2 The Origin of Graphic Representation in Physiology
26.3 The Kymograph and the Birth of Modern Physiology
26.4 First Recording of Intestinal Mechanical Events Using the Kymograph
26.5 Isolated Preparations of the Intestine
26.6 X-Rays in Gastroenterology at the Turn of the Twentieth Century
26.7 Direct Visual Recording In Vivo
26.8 Spatiotemporal Maps of Changes in Diameter (DMaps) and Length from Videos
26.9 Spatiotemporal Maps of Diameters In Vivo: The Challenges
26.9.1 Videos
26.9.2 Fluoroscopy
26.9.3 Ultrasonography: Photoacoustic Imaging (PA)
26.9.4 Magnetic Resonance Imaging (MRI)
26.10 Spatiotemporal Maps of Changes in Forces (PMaps)
26.10.1 Myoelectrical Activity and Its Mechanical Equivalence
26.10.2 Calcium Waves in Smooth Muscle and Pacemaker Cells
26.10.3 Recording Forces of Contractions
26.10.3.1 Intraluminal Balloons
26.10.3.2 Force Transducers
26.10.3.3 Strain Gauges
26.10.3.4 Multiple Manometry: The Birth of PMaps
26.11 Examples of Kinetic and Kinematic Recordings Combined
26.11.1 Earlier Combinations of Recording Methods
26.11.2 Full Combination of Kinematics and Kinetics: DPMaps
26.11.3 Combining Kinetics, Kinematics Forces and Flow, Propulsion and Transit Times
26.12 Concluding Remarks
References
27: Rhythmicity in the Enteric Nervous System of Mice
27.1 Introduction
27.2 Motor Patterns in Mouse Colon
27.3 Sensitivity to Distension of CMCs
27.4 Potential Role of Endogenous 5HT from the Mucosa in Cyclical Neurogenic Motor Patterns
27.5 Coordinated Rhythmic Firing of Myenteric Neurons During CMCs Revealed by Neuronal Imaging of the ENS
27.6 Distinct Physiological Motor Patterns in the Mouse Colon
27.7 What Mechanisms Underlie Aboral Propulsion?
27.8 Rhythmic Activity of Myenteric Neurons During Propulsive Motor Patterns in the Mouse Colon
27.9 Are There ENS Pacemaker Neurons That Could Underlie the Rhythmic Generation of CMCs?
27.10 Comparison with Other Species
27.11 Conclusion
References
28: The Shaggy Dog Story of Enteric Signaling: Serotonin, a Molecular Megillah
28.1 The History of 5-HT
28.2 5-HT and the Peristaltic Reflex
28.3 Did Bülbring Make a Mistake?
28.4 5-HT Is Essential for Mucosal Stimulation to Evoke the Peristaltic Reflex, But 5-HT Is Not Essential for Reflexes That Mechanosensitive Nerve Fibers Induce
28.5 Luminal Microbes Use EC Cells and 5-HT to Regulate the ENS
28.6 5-HT Is a Growth Factor for Enteric Neurons
28.7 SERT Plays a Critical Role in Enteric 5-HT Signaling
28.8 Inhibition of VMAT2
28.9 SERT Regulates Enteric Serotonergic Signaling
28.10 The Importance of Extraenteric TPH1 During Early Development
28.11 Tryptamine
28.12 Summary and Conclusions
References
29: Upper Gastrointestinal Motility, Disease and Potential of Stem Cell Therapy
29.1 Introduction
29.2 Normal Motility in the Upper GI Tract: Esophagus and Stomach
29.2.1 Esophagus
29.2.2 Stomach
29.3 Upper GI Dysfunction at the Lower Esophageal and Pyloric Sphincters
29.3.1 Esophageal Achalasia
29.3.2 Gastroparesis
29.4 Advances in Cell Replacement of nNOS Neurons
29.5 Analysis of Neural Function and Network Integration
29.6 Protocols for Generation of ENS-Like Cells from iPSCs
29.7 Conclusion
References
30: Epithelial 5-HT4 Receptors as a Target for Treating Constipation and Intestinal Inflammation
30.1 Expression of 5-HT4 Receptors by Colonic Epithelial Cells and Effects of Their Stimulation on Motility and Nociception [4]
30.2 Attenuation of Colitis by Luminally Administered 5-HT4 Agonists [12]
30.3 Prokinetic Effects of Luminally Acting 5-HT4 Receptor Agonists [8]
30.4 Concluding Remarks
References
Index