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.
Butera
R J
RJ
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.
Rinzel
J
J
Smith
J C
JC
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