Reprinted from HANDBOOK OF PHYSIOLOGY -- THE NERVOUS SYSTEM IV Printed in U. S. A. CHAPTER 9 Neurophysiology of breathing in mammals JACK L. FELDMAN Departments of Physiology and Anesthesia, Northwestern University, Chicago, Illinois CHAPTER CONTENTS Respiratory Homeostasis and Control of Respiratory Movements Effectors of ventilation Respiratory movements Respiratory motoneuronal outflow Respiratory muscles and their innervation Diaphragm and phrenic motoneurons Intercostal muscles and motoneurons Laryngeal and pharyngeal muscles and motoneurons High-frequency oscillations Summary Central Location of Respiratory Controller Historical background Lesions Stimulation Anatomy Neuron recording Summary Modern view Spinal cord genesis of respiratory movements? Brain stem respiratory neurons Brain stem anatomy Medulla Pons Classification of respiratory neurons Patterns of respiratory neuron discharge Connections between respiratory neurons Intramedullary connections Ventral surface connections Pontomedullary connections Bulbospinal connections Importance of connections between hemimedullae Location and mechanisms for generation of respiratory patterns Production of respiratory pattern Pontine respiratory group Dorsal and ventral respiratory groups Central pattern generation and respiration Mechanisms for rhythmogenesis Perturbations and network models for respiratory pattern generation Interactions among respiratory neurons Mechanisms underlying generation of augmenting inspiratory and expiratory activity Generation of phase transitions Possible mechanisms underlying phase transitions Summary Hypothesis for role of dorsal and ventral respiratory groups in generating respiratory pattern Sensors Time course of responses to respiratory afferent stimulation Integrated responses to changes in carbon dioxide Intracranial carbon dioxide reception-phenomenology of ventral surface Critique Neuronal response to hyper- and hypocapnia; a caveat Spinal motoneurons Laryngeal motoneurons Dorsal-ventral respiratory group neurons Ventral medullary neurons Integrated responses to changes in oxygen Heymans type (arterial) chemoreceptors Effects of oxygen on medullary respiratory neurons Summary Mechanoreceptors Pulmonary stretch receptors Inspiratory shortening reflex Laryngeal pattern Responses of brain stem inspiratory neurons to activation of lung stretch receptors Expiratory facilitatory reflex and control of expiratory duration Responses of expiratory neurons to lung inflations Summary Exercise-An Example of an Integrated Response Critique State Dependence Conclusion MOVEMENT OF THE RESPIRATORY musculature re- sults in airflow into and out of the lung. Control of this movement is critical for metabolic and acid-base equilibrium (231) and is important in behavior. The neural mechanisms controlling these respiratory movements comprise an extremely reliable system that works continuously and efficiently throughout life. This chapter focuses on the neurophysiology of the automatic rhythmic movements of the respiratory musculature necessary for homeostatic alveolar ven- tilation in mammals. An important goal in respiratory neurobiology is to explain the generation and control of respiratory pat- tern in terms of the biophysical, synaptic, and network properties of identified groups of neurons in the CNS. A fundamental aspect of this problem is to explain the generation of the rhythmic alteration of activity and silence in respiratory motoneurons in terms of the properties of CNS neurons that have respiratory- related patterns of activity. Of particular interest is 463