An ionic current model for medullary respiratory neurons

Neurons of the mammalian medullary respiratory center have complex patterns of electrophysiological behavior. Three typical phenomena associated with these patterns are spike frequency adaptation (SFA), delayed excitation (DE ), and postinhibitory rebound (PIR). Although several nuclei are associated with the medullary-pontine respiratory center, we focused on neurons from two nuclei: (1) the ventral subnucleus of the nucleus tractus solitarius (v NTS) of the dorsal respiratory group and (2) the nucleus ambiguus (NA) of t he ventral respiratory group. We developed a Hodgkin-Huxley (HH) type model of the typical medullary neuron that is capable of mimicking the discharge pattern of real neurons to a very high degree. Closer examination of typic al data revealed, however, that there was not one type of medullary respira tory neuron, but at least three (types A, B-1, and B-2). We classified thes e neurons based on the electrophysiologic phenomena that they exhibited (ty pe A exhibits DE but not PIR; types B-1 and B-2 exhibit PIR but not DE; all types are adapting). Our objective was to relate each of these well-known phenomena to specific ionic current mechanisms. In the model, three current s directly affect the phenomena investigated: the Ca2+-activated K+ current , I-K,I-Ca, controls peak and steady-state firing rates and the time consta nt of adaptation; the transient outward K+ current, I, is responsible for a ll aspects of DE, including the dependence of delay on the magnitude and du ration of conditioning hyperpolarization; and the hyperpolarization-activat ed current, I, elicits PIR and dictates its dependencies. We consider that our HH model represents a unifying structure, whereby different electrophys iological phenomena or discharge patterns can be emulated using different s trengths of the component ionic membrane currents (particularly I-K,I-Ca, I , and I). Moreover, its predictions suggest that the electrophysiological c haracteristics of medullary respiratory neurons, from different areas of th e brainstem and even from different species, can be modeled using the same structural framework, wherein the specific properties of individual neurons are emulated by adjusting the strengths of key ionic membrane currents in the model.