Figure 7. Modeling preBötC MOR activation in silico.

(A) Example model network structure. Model networks were connected randomly and contained excitatory (80%) and inhibitory neurons (20%) that were intrinsically tonic (35%) or quiescent (65%). Half of all excitatory neurons were designated as Oprm1+. Node size and centrality represent the number of synaptic connections. (B) Current/voltage plots for intrinsically tonic (n=17) and quiescent (n=31) Oprm1+ model neurons for the applied opioid-driven hyperpolarization. (C) Example rhythmic activity from the network shown in (A) at baseline, during 6 pA hyperpolarization of Oprm1+ neurons, and during 6 pA hyperpolarization and a 45% reduction in pre-synaptic efficacy of Oprm1+ neurons. Orange asterisks indicate burst failures. (D) Heat maps showing the isolated and combined effects of Oprm1+ neuron hyperpolarization and pre-synaptic suppression on characteristics of the network rhythm. (E) Example spiking activity of all 300 neurons in the model network at baseline and during simulated MOR activation (6 pA hyperpolarization and 45% pre-synaptic suppression of Oprm1+ neurons). (F) Quantified inter-burst interval (IBI) spike frequencies of intrinsically tonic and quiescent Oprm1+ and Oprm1− neurons during simulated MOR activation. (G) Spike frequency during network bursts for all Oprm1+ and Oprm1- model neurons during simulated MOR activation (combined effect of 1 designates 6 pA hyperpolarization and 55% pre-synaptic efficacy of Oprm1+ neurons). Data shown as mean± SE.

Figure 7—figure supplement 1. A simulated data-driven Oprm1+ subpopulation is necessary for rhythmogenesis in an in silico preBötC model network.

(A) Example integrated population activity and spike rasters at baseline and during blockade of pre-synaptic transmission from Oprm1+ neurons (${\displaystyle sy{n}_{opioid}}$=0) with and without inhibitory synaptic interactions (inhibition block). (B) Example integrated population activity and spike rasters at baseline and during a strong hyperpolarization (${\displaystyle I_{opioid}}$=9pA) of Oprm1+ neurons with and without concurrent blockade of inhibitory synapses. (C) Expanded view of integrated rhythmic activity and corresponding spike rasters of all 300 model neurons during baseline (left), Oprm1+ pre-synaptic block (middle), and strong Oprm1+ hyperpolarization (right). Note that in both cases the network rhythm is silenced despite distinct effects on the spiking activity of Oprm1+ neurons.

Figure 7—figure supplement 2. OIRD in the preBötC is best modeled by concurrent hyperpolarization and pre-synaptic suppression of a simulated Oprm1+ subpopulation.

(A) Rhythmic activity of a representative model network during independent or concurrent Oprm1+ neuron hyperpolarization and/or pre-synaptic suppression. (B) Expanded view of network activities shown in (A) and corresponding spiking activity from all 300 model neurons.