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Role and limits of inhibition in an excitatory burst generator Harris, Kameron


The pre-Botzinger complex (preBot) is now recognized as the essential core of respiratory rhythm generation, where it generates the inspiratory phase. Rhythmogenesis occurs through network synchronization. Using a biophysical model of the entire preBot, we ask: What is the role of inhibitory cells in the preBot? How does changing the sparsity of connections and synaptic strengths affect the resulting rhythm? These modeling results are compared to in vitro slice experiments in which we progressively block inhibitory and excitatory synaptic transmission. We find that too much sparsity or inhibition disrupts rhythm generation, yet highly connected networks without inhibition also produce non-biological rhythms. Our slice experiments suggest that the real preBot lies within the partially synchronized region of network parameter space. As inhibitory neurons are added to the network, some cells fire out-of-phase with the main population rhythm, which offers an explanation for the out-of-phase cells observed in preBot. However, it is not possible to produce a two-phase population rhythm in our model without adding further structure to the network. The preBot and Botzinger complexes therefore require structured networks in order to produce alternating inspiratory and expiratory rhythms. Finally, we present preliminary stages of a spin model for oscillator phases which reproduces the qualitative features of the synchronization transition.

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