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.
Cellular and Systems Neurobiology Section, Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455, USA.
R J
RJ
Butera
J
J
Rinzel
J C
JC
Smith
D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000502:physiology*; D003198:Computer Simulation; D066298:In Vitro Techniques; D008322:Mammals; D008526:Medulla Oblongata / Q000502:physiology*; D008564:Membrane Potentials; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D009991:Oscillometry; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D015656:Respiratory Mechanics / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D015221:Potassium Channels; D015222:Sodium Channels