Dynamics of excitatory networks of bursting pacemaking neurons: Modeling and experimental studies of the respiratory central pattern generator

Abstract We have explored the dynamics of a computational model of an excitatory network of bursting pacemaker neurons with heterogeneous properties. The network generates synchronous bursts of activity, and the frequency of both single cells and the synaptically coupled pacemaker cell population may be controlled by varying the degree of depolarizing input (DI). The dynamic range of DI where stable bursting occurs is significantly larger for the coupled population than that of individual cells, suggesting a functional role of cellular heterogeneity in making biological rhythms more robust. Experimental evidence is presented from the pacemaker-network generating the respiratory rhythm in the mammalian brainstem.

[1]  K. Ballanyi,et al.  Synaptic inhibition in the isolated respiratory network of neonatal rats , 1998, The European journal of neuroscience.

[2]  J C Smith,et al.  Generation and transmission of respiratory oscillations in medullary slices: role of excitatory amino acids. , 1993, Journal of neurophysiology.

[3]  T. Suzue,et al.  Respiratory rhythm generation in the in vitro brain stem‐spinal cord preparation of the neonatal rat. , 1984, The Journal of physiology.

[4]  J. Ramirez,et al.  Postnatal changes in the mammalian respiratory network as revealed by the transverse brainstem slice of mice. , 1996, The Journal of physiology.

[5]  J. Feldman,et al.  PreBötzinger complex and pacemaker neurons: hypothesized site and kernel for respiratory rhythm generation. , 1998, Annual review of physiology.

[6]  Ilya A. Rybak,et al.  Modeling neural mechanisms for genesis of respiratory rhythm and pattern. I. Models of respiratory neurons. , 1997, Journal of neurophysiology.

[7]  J C Smith,et al.  Pre-Bötzinger complex in the cat. , 1995, Journal of neurophysiology.

[8]  Jeffrey C. Smith,et al.  Neuronal pacemaker for breathing visualized in vitro , 1999, Nature.

[9]  J. C. Smith,et al.  Cellular Mechanisms Underlying Modulation of Breathing Pattern in Mammals a , 1989, Annals of the New York Academy of Sciences.

[10]  Allan I. Pack,et al.  Computational Aspects of the Respiratory Pattern Generator , 1994, Neural Computation.

[11]  C. Trouth.  Ventral Brainstem Mechanisms and Control of Respiration and Blood Pressure , 1995 .

[12]  J. Ramirez,et al.  The hypoxic response of neurones within the in vitro mammalian respiratory network , 1998, The Journal of physiology.

[13]  J. C. Smith,et al.  Models of respiratory rhythm generation in the pre-Bötzinger complex. II. Populations Of coupled pacemaker neurons. , 1999, Journal of neurophysiology.

[14]  J C Smith,et al.  Pacemaker behavior of respiratory neurons in medullary slices from neonatal rat. , 1994, Journal of neurophysiology.

[15]  D. Richter.  Neural Regulation of Respiration: Rhythmogenesis and Afferent Control , 1996 .

[16]  P. Guyenet,et al.  NTS neurons with carotid chemoreceptor inputs arborize in the rostral ventrolateral medulla. , 1996, The American journal of physiology.

[17]  Paul S. G. Stein.  Neurons, networks, and motor behavior , 1999 .

[18]  J C Smith,et al.  Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity. , 1990, Journal of neurophysiology.

[19]  J. C. Smith,et al.  Models of respiratory rhythm generation in the pre-Bötzinger complex. I. Bursting pacemaker neurons. , 1999, Journal of neurophysiology.

[20]  J. Champagnat,et al.  Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters. , 1995, Physiological reviews.

[21]  J. C. Smith,et al.  Pre-Bötzinger complex: a brainstem region that may generate respiratory rhythm in mammals. , 1991, Science.

[22]  I. Rybak,et al.  Modeling neural mechanisms for genesis of respiratory rhythm and pattern. II. Network models of the central respiratory pattern generator. , 1997, Journal of neurophysiology.

[23]  Diethelm W. Richter,et al.  Mechanisms of respiratory rhythm generation , 1992, Current Opinion in Neurobiology.