The dynamic range of bursting in a model respiratory pacemaker network

A network of excitatory neurons within the pre-Botzinger complex (pre-BotC) of the mammalian brain stem has been found experimentally to generate robust, synchronized population bursts of activity. An experimentally calibrated model for pre-BotC cells yields typical square-wave bursting behavior in the absence of coupling, over a certain parameter range, with quiescence or tonic spiking outside of this range. Previous simulations of this model showed that the introduction of synaptic coupling extends the bursting parameter range significantly and induces complex effects on burst characteristics. In this paper, we use geometric dynamical systems techniques, predominantly a fast/slow decomposition and bifurcation analysis approach, to explain these effects in a two-cell model network. Our analysis yields the novel finding that, over a broad range of synaptic coupling strengths, the network can support two qualitatively distinct forms of synchronized bursting, which we call symmetric and asymmetric bursting, as well as both symmetric and asymmetric tonic spiking. By elucidating the dynamical mechanisms underlying the transitions between these states, we also gain insight into how relevant parameters influence burst duration and interburst intervals. We find that, in the two-cell network with synaptic coupling, the stable family of periodic orbits for the fast subsystem features spike asynchrony within otherwise synchronized bursts and terminates in a saddle-node bifurcation, rather than in a homoclinic bifurcation, over a wide parameter range. As a result, square-wave bursting is replaced by what we call top hat bursting ( also known as fold/fold cycle bursting), at least for a broad range of parameter values. Further, spike asynchrony is a key ingredient in shaping the dynamic range of bursting, leading to a significant enhancement in the parameter range over which bursting occurs and an abrupt increase in burst duration as an appropriate parameter is varied.