Rhythmic Bursting in the Pre-Botzinger Complex: Mechanisms and Models

The pre-Botzinger complex (pre-BotC), a neural structure involved in respiratory rhythm generation, can generate rhythmic bursting activity in vitro that persists after blockade of synaptic inhibition. Experimental studies have identified two mechanisms potentially involved in this activity: one based on the persistent sodium current (I-NaP) and the other involving calcium (I-Ca) and/or calcium-activated nonspecific cation (I-CAN) currents. In this modeling study, we investigated bursting generated in single neurons and excitatory neural populations with randomly distributed conductances of I-NaP and I-Ca. We analyzed the possible roles of these currents, the Na+/K+ pump, synaptic mechanisms, and network interactions in rhythmic bursting generated under different conditions. We show that a population of synaptically coupled excitatory neurons with randomly distributed I-NaP-and/or I-CAN-mediated burst generating mechanisms can operate in different oscillatory regimes with bursting dependent on either current or independent of both. The existence of multiple oscillatory regimes and their state dependence may explain rhythmic activities observed in the pre-BotC under different conditions.