Models of Neuronal Bursting Behavior: Implications for In-Vivo Versus In-Vitro Respiratory Rhythmogenesis

Abstract

Neonatal in-vitro preparations can generate respiratory-like oscillations based on the intrinsic bursting or pacemaker properties in some neurons within the medullary preBötzinger complex (PBC)^1-3. This discovery provided a basis for a hybrid pacemaker-network theory that suggests that pacemaker PBC neurons form a kernel of the central pattern generator and hence provide a necessary contribution to the genesis of the respiratory rhythm⁴. However, it is controversial whether a pacemaker-based mechanism necessarily operates in vivo. Specifically, the pacemaker-based models face principal problems in providing explanations to systems-level phenomena such as an independent regulation of respiratory phases, respiratory reflexes (e.g. the Hering-Breuer reflex), various phase resetting phenomena. On the other hand, the network theories and models based on in-vivo data can explain these phenomena^5,6, but demand the respiratory phase transitions to be based on the reciprocal inhibitory interactions between respiratory neurons. Therefore, the network-based models have so far been unable to explain a pacemaker-driven rhythm recorded in vitro which is resistant to blockade of synaptic inhibition⁷. The current state of knowledge in the field requires a comprehensive computational study of the relationships between in-vivo and in-vitro data. The objective of this study was to explore the concept that the respiratory network can generate a breathing pattern by either a network or a hybrid pacemaker-network mechanism, which is state-dependent.