Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model

摘要

An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current (INaP) and a calcium-activated non-selective cationic current (ICAN)—were proposed to individually or in combination generate cellular- and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles in a model of a synaptically connected population of excitatory neurons with ICAN and INaP. This model robustly reproduces experimental data showing that rhythm generation can be independent of ICAN activation, which determines population activity amplitude. This occurs when ICAN is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on INaP in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms.