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Models of respiratory rhythm generation in the pre-Bötzinger complex. I. Bursting pacemaker neurons.

A network of oscillatory bursting neurons with excitatory coupling is hypothesized to define the primary kernel for respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC) in mammals. Two minimal models of these neurons are proposed. In model 1, bursting arises via fast activation and slow inactivation of a persistent Na+ current INaP-h. In model 2, bursting arises via a fast-activating persistent Na+ current INaP and slow activation of a K+ current IKS. In both models, action potentials are generated via fast Na+ and K+ currents. The two models have few differences in parameters to facilitate a rigorous comparison of the two different burst-generating mechanisms. Both models are consistent with many of the dynamic features of electrophysiological recordings from pre-BötC oscillatory bursting neurons in vitro, including voltage-dependent activity modes (silence, bursting, and beating), a voltage-dependent burst frequency that can vary from 0.05 to >1 Hz, and a decaying spike frequency during bursting. These results are robust and persist across a wide range of parameter values for both models. However, the dynamics of model 1 are more consistent with experimental data in that the burst duration decreases as the baseline membrane potential is depolarized and the model has a relatively flat membrane potential trajectory during the interburst interval. We propose several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.

Pubmed ID: 10400966

Authors

  • Butera RJ
  • Rinzel J
  • Smith JC

Journal

Journal of neurophysiology

Publication Data

July 10, 1999

Associated Grants

None

Mesh Terms

  • Animals
  • Animals, Newborn
  • Biological Clocks
  • Computer Simulation
  • In Vitro Techniques
  • Mammals
  • Medulla Oblongata
  • Membrane Potentials
  • Models, Neurological
  • Neurons
  • Oscillometry
  • Potassium Channels
  • Rats
  • Respiratory Mechanics
  • Sodium Channels