Interactions of persistent sodium and calcium-activated nonspecific cationic currents yield dynamically distinct bursting regimes in a model of respiratory neurons

The preBötzinger complex (preBötC) is a heterogeneous neuronal network within the mammalian brainstem that has been experimentally found to generate robust, synchronous bursts that drive the inspiratory phase of the respiratory rhythm. The persistent sodium (NaP) current is observed in every preBötC neuron, and significant modeling effort has characterized its contribution to square-wave bursting in the preBötC. Recent experimental work demonstrated that neurons within the preBötC are endowed with a calcium-activated nonspecific cationic (CAN) current that is activated by a signaling cascade initiated by glutamate. In a preBötC model, the CAN current was shown to promote robust bursts that experience depolarization block (DB bursts). We consider a self-coupled model neuron, which we represent as a single compartment based on our experimental finding of electrotonic compactness, under variation of gNaP, the conductance of the NaP current, and gCAN, the conductance of the CAN current. Varying these two conductances yields a spectrum of activity patterns, including quiescence, tonic activity, square-wave bursting, DB bursting, and a novel mixture of square-wave and DB bursts, which match well with activity that we observe in experimental preparations. We elucidate the mechanisms underlying these dynamics, as well as the transitions between these regimes and the occurrence of bistability, by applying the mathematical tools of bifurcation analysis and slow-fast decomposition. Based on the prevalence of NaP and CAN currents, we expect that the generalizable framework for modeling their interactions that we present may be relevant to the rhythmicity of other brain areas beyond the preBötC as well.