Computational modeling of opioid-induced respiratory depression

The Pre-Bötzinger complex (preBötC), a neuronal network located in the medulla, is a central pattern generator that facilitates breathing rhythm. Opioid-based drugs have the ability to cause significant decreases in the frequency of the rhythm, thereby shutting down the network and causing opioid-induced respiratory depression (OIRD). To explore the neural dynamics of this phenomenon, we used a computational model of OIRD to perform several in-silico experiments that manipulate the network topology and simulate potential drug treatments to protect the respiratory rhythm against OIRD. We found that (1) resistance to opioids is variable across randomly generated networks based on connectivity, (2) the recruitment of quiescent neurons is extremely important for maintaining the rhythm, and (3) the perturbation of persistent sodium current conductance and leak current conductance are both provide effective protection against OIRD.