Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model

We review a new unified model of respiratory rhythm generation - the hybrid pacemaker-network model. This model represents a comprehensive synthesis o f cellular and network mechanisms that can theoretically account for rhythm generation in different functional states, from the most reduced states in the neonatal nervous system in vitro to the intact adult system in vivo. T he model incorporates a critical neuronal kernel consisting of a network of excitatory neurons with state-dependent, oscillatory bursting or pacemaker properties. This kernel: located in the pre-Botzinger complex of the ventr olateral medulla, provides a rudimentary pacemaker network mechanism for ge nerating an inspiratory rhythm, revealed predominately in functionally redu ced states in vitro. In vivo the kernel is embedded in a larger network tha t interacts with the kernel via inhibitory synaptic connections that provid e the dynamic control required for the evolution of the complete pattern of inspiratory and expiratory network activity. The resulting hybrid of cellu lar pacemaker and network properties functionally endows the system with mu ltiple mechanisms of rhythm generation. New biophysically realistic mathema tical models of the hybrid pacemaker-network have been developed that illus trate these concepts and provide a computational framework for investigatin g interactions of cellular and network processes that must be analyzed to u nderstand rhythm generation. (C) 2000 Elsevier Science B.V, All rights rese rved.