Neurogastroenterology and Motility: General Principles UTP 36

Table of Contents General Digestive Motility Involves Integrated Function of Multiple Tissues and Types of Cells Muscle Physiology Smooth Muscles are Classified as Unitary Or Multi-Unit Types Structure and Function of Circular Muscle of Muscularis Externa Differs From Longitudinal Electro- and Pharmaco-Mechanical Coupling are Mechanisms For Triggering Contractions in Gastrointestinal Muscles Cross-Bridge Formation and Sliding of Actin and Myosin Filaments Account For Contraction of Gastrointestinal Muscle Length-Tension Relations For Smooth Muscle are Like Skeletal Muscle and Reflect A Sliding Filament Mechanism of Contraction Thick and Thin Contractile Filaments in Smooth Muscle Have Different Chemical Composition Multiple Biochemical Steps are Involved in Cross-Bridge Cycling in Smooth Muscle Multiple Mechanisms Maintain Cytoplasmic Ca2+ Levels For Smooth Muscle Contraction Cholecystokinin Has Different Effects on Inositol 1,4,5 Trisphosphate in Intestinal Circular and Longitudinal Muscle Electrical Slow Waves in Gastrointestinal Muscles Occur in Four Phases Determined By Specific Ionic Mechanisms Electrical Activity Occurs at Different Frequencies in Stomach, Small Intestine and Colon Electrical Slow Waves Without Action Potentials are Often Present in The Small Intestine Phasic Contractions are Seen When Action Potentials Appear on Electrical Slow Waves in Extracellular Electrical Records Interstitial Cells of Cajal Form Networks That Contact The Gastrointestinal Musculature Interstitial Cells of Cajal are Relays For Transmission From Enteric Motor Neurons to The Gastrointestinal Musculature Pacemakers For Electrical Slow Waves are at The Submucosal and Myenteric Borders of The Circular Muscle Gastrointestinal and Esophageal Smooth Muscles Have Properties of A Functional Electrical Syncytium Autonomic Neurobiology A Hierarchy of Neural Integrative Centers Determines Moment-to- Moment Motor Behavior of The Digestive Tract Synaptic Transmission, Paracrine Signaling and Hormonal Signaling are Forms of Chemical Information Transfer in The Digestive Tract Three Divisions of The Autonomic Nervous System Innervate The Digestive Tract Neurons of The Autonomic Parasympathetic Division Project From The Medulla Oblongata and Sacral Regions of The Spinal Cord Cell Bodies of Efferent Vagal Neurons are in The Dorsal Motor Nucleus of The Brain Stem Neurons of The Autonomic Sympathetic Division Project to The Gut From Thoracic and First Lumbar Segments of The Spinal Cord Vagal Nerves Transmit Sensory Information to The Brain and Parasympathetic Efferent Signals to The Digestive Tract Splanchnic Nerves Transmit Sensory Information to The Spinal Cord and Efferent Sympathetic Signals to The Digestive Tract The Enteric Nervous System Functions as A Brain-In-The-Gut Feedback Control of Gastrointestinal Effector Systems Is A Function of The Enteric Nervous System The Enteric Nervous System Consists of Myenteric and Submucous Plexuses Sensory Neurons, Interneurons and Motor Neurons are Synaptically Interconnected to Form The Microcircuits of The Enteric Nervous System Dogiel Types I and Ii are The Principal Morphological Classes of Enteric Neurons Dogiel Types I and Ii Enteric Neurons Have Specific Neurotransmitters and Directionality of Projections Multiple Criteria are Used in The Classification of Enteric Neurons Neurochemical Coding Identifies Functional Classes and Projections of Enteric Neurons Enteric Neurons: Electrophysiologic Behavior Intracellular Recording Is Used to Study Electrical and Synaptic Behavior of Enteric Neurons Three Kinds of Electrical Events Can Be Recorded in Cell Bodies of Enteric Neurons Field Stimulation, Stimulation of Neurites and Intraneuronal Current Injection are Used to Evoke Action Potentials in Enteric Neurons S- and Ah-Type Enteric Neurons are Distinguished By Their Electrical Behavior Long Lasting After-Hyperpolarization Lengthens The Refractory Period in Ah-Type Enteric Neurons Repetitive Action Potential Discharge Occurs in S-Type But Not in Ah-Type Enteric Neurons Anodal-Break Excitation Occurs in S-Type But Not in Ah-Type Enteric Neurons Tetrodotoxin (Ttx) Abolishes Action Potentials in S-Type But Not in Ah-Type Enteric Neurons Enteric Neurons Discharge Spontaneously in Bursts Or Single Spike Patterns Synaptic Transmission Multiple Kinds of Synaptic Events Occur in The Enteric Microcircuits Fast and Slow Excitatory (Epsps) and Slow Inhibitory Postsynaptic Potentials (Ipsp) Occur in Enteric Neurons Fast Excitatory Postsynaptic Potentials (Epsp) in The Enteric Nervous System Have Specific Properties Fast Excitatory Postsynaptic Potentials (Epsps) Evoke Action Potentials When Depolarization of The Membrane Exceeds Threshold Enteric Slow Excitatory Postsynaptic Potentials (Epsps) Have Specific Properties Slow Excitatory Postsynaptic Potentials Generate Long- Lasting Trains of Action Potentials Depolarization and Increased Resistance Occurs During Enteric Slow Synaptic Excitation Hyperpolarizing After-Potentials in Ah-Type Neurons are Suppressed During Slow Synaptic Excitation Receptors For Multiple Signal Substances are Linked to The Cellular Mechanism For Slow Synaptic Excitation Slow Synaptic Excitation Involves Stimulation of Adenylate Cyclase Slow Excitatory Synaptic Transmission (Epsp) Is A Mechanism For Prolonged Neural Excitation Or Inhibition of Gi Effectors Slow Synaptic Excitation (Epsp) Is A Mechanism For Gating Directional Spread of Action Potentials in Dogiel Ii Neurons Enteric Slow Inhibitory Postsynaptic Potentials Have Specific Properties Slow Inhibitory Postsynaptic Potentials (Ipsp) are Hyperpolarizing Potentials Slow Inhibitory Post Synaptic Potentials are Produced By Multiple Signal Substances and Receptor Subtypes Presynaptic Inhibitory Receptors are Found at Enteric Synapses and Neuromuscular Junctions Multiple Types of Pre-Synaptic Or Pre-Junctional Inhibitory Receptors are Found in The Enteric Nervous System Presynaptic Facilitation Enhances Release of Neurotransmitter and Increases Amplitude of Excitatory Postsynaptic Potentials Cisapride Acts Presynaptically to Enhance The Amplitude of Epsps at Enteric Nicotinic Synapses Enteric Motor Neurons are Final Pathways From The Enteric Nervous System to The Gastrointestinal Musculature Enteric Motor Axons Have Varicosities Where Neurotransmitters are Stored and Released Nitric Oxide (No) Is An Inhibitory Neurotransmitter in The Digestive Tract Musculature Nitric Oxide (N0) and Vasoactive Intestinal Peptide (Vip)Interact as Inhibitory Neurotransmitters in The Digestive Musculature Activity of A Subpopulation of Inhibitory Motor Neurons to The Intestinal Circular Muscle Tonically Inhibits Contraction Strength of Circular Muscle Contraction Evoked By Each Slow Wave Cycle Is A Function of The Number of Inhibitory Motor Neurons in An Active State Inhibitory Innervation of Gastrointestinal Sphincters Is Transiently Activated For Timed Opening and Passage of Luminal Contents Inhibitory Motor Innervation of The Intestinal Circular Muscle Is Continuously Active and Is Transiently Inactivated to Permit Muscle Contraction The Directional Sequence in Which Inhibitory Motor Neurons are Inactivated Determines Oral Or Aboral Propagation of Contractions Feedforward Transmission of Slow Epsps in Driver Circuits Is A Mechanism For Simultaneous Activation of Motor Neuron Pools Slow Synaptic Excitation (Slow Epsp) Underlies A Somal Gating Mechanism For Rapid Activation of Enteric Driver Circuits Ah/Dogiel Type Ii Enteric Neurons are Important Functional Elements in The Microcircuitry of The Brain-in-The-Gut Chronic Intestinal Pseudoobstruction Can Be Myopathic Or Neuropathic Familial Visceral Myopathic Is A Degenerative Disease of Smooth Muscle That Leads to Pseudoobstruction Hypoactive Motility Occurs in Myopathic Forms of Chronic Intestinal Pseudoobstruction Acquired Loss of Enteric Inhibitory Motor Neurons Leads to Uncontrolled Myogenic Contractions and Chronic Intestinal Pseudoobstruction A Mutant Recessive Gene Results in Piebald Coat Coloration and Congenital Megacolon (Hirschsprung's Disease) in The Mouse In The Absence of The Enteric Nervous System, Myogenic Mechanisms Lead to Tonic Contracture and Pseudoobstruction Loss of Inhibitory Motor Neurons to Smooth Muscle Sphincters Results in Achalasia Disinhibitory Motor Disease Is An Enteric Neuropathy That Reflects Loss of Inhibitory Motor Neurons and Produces Pseudoobstruction Autoimmune Attack on Enteric Neurons in Paraneoplastic Syndrome Leads to Chronic Intestinal Pseudoobstruction Sensory Neurophysiology Multiple Kinds of Sensory Receptors are Present in The Digestive Tract Release of Serotonin (5-Ht) From Enterochromaffin Cells Is An Early Step in Transduction of Sensory Information Enteroendocrine Cells are The First Step in The Transduction of Chemoreceptive Sensory Information Chemoreceptors For Acid in The Gastric Or Duodenal Mucosa Evoke Firing in Vagal Afferents High and Low Threshold Enteric Mechanosensitive Neurons Project Sensory Information From The Large Intestine to The Spinal Cord Convergence of Somatic and Visceral Afferents in The Spinalcord Accounts For Referral of Visceral Pain to Cutaneous Sites Distension of The Esophagus Evokes Firing in Vagal Afferent Fibers Distension of The Esophagus By Balloon Inflation Evokes Stereotypic Brain Wave Patterns Silent Gastrointestinal Afferents are Sensitized By Inflammation Activity in The Low-Threshold Class of Visceral Afferents Accounts For Normal Regulatory Functions Activation of High-Threshold Afferents Leads to Acute Pain and Recruitment of Silent Nociceptive Afferents Produces Chronic Pain Abdominal Pain Balloon Distension in The Colon Evokes Pain Referred to Specific Abdominal Regions Balloon Distension in The Upper Digestive Tract Evokes Pain Referred to Specific Cutaneous Regions Individuals With The Irritable Bowel Syndrome Have Increased Sensitivity to Balloon Distension in The Large Intestine Anterior Cingulate Cortex and Surrounding Regions are Implicated in Pain Sensations Sympathetic Nervous System Sympathetic Nerve Stimulation Inhibits Motility and Secretion and Contracts Smooth Muscle Sphincters Norepinephrine Released From Sympathetic Nerves Acts By Presynaptic Inhibition to Inactivate The Enteric Neural Circuits Sympathetic Prevertebral Ganglia are in Pathways For Rapid Transfer of Signals Between Separated Regions of Bowel Prevertebral Sympathetic Ganglia and Intermesenteric Nerves (Imn) Transmit Signals For Entero-Enteric Inhibition of Intestinal Motility Parasympathetic Nervous System Signals Transmitted to The Enteric Nervous System By Vagal and Pelvic Nerves May Result in Contraction Or Relaxation of Digestive Musculature Flow of Signals in The Brain-Gut Axis Is Directional Oxytocin and Thyrotropin Releasing Hormone (Trh) are Neurotransmitters in Central Neural Control Circuits For Gastric Motility Vago-Vagal Reflex Circuits Consist of Sensory Afferents, Second Order Interneurons and Efferent Neurons Vago-Vagal Reflex Circuits Receive Inputs From Higher Brain Centers Brain-Gut Axis Hormonal Modulation in The Brain-Gut Axis: Pancreatic Polypeptide Suppresses Vagal Outflow to The Pancreas Mood Changes in Humans Alters The Appearance of The Gastric Mucosa Stress-Induced Alterations in Multiple Gastric Alterations in Large Intestinal Motility and Blood Flow Occur in Response to Acute Stress in Humans Cerebral Thyrotropin Releasing Hormone (Trh) and Corticotropin Releasing Hormone (Crh) are Chemical Signals in Brain-Gut Responses to Stress Back to Unit 36