Pacific Institute for the Mathematical Sciences - PIMS

Emergent network properties in the preBotzinger Complex: the cellular and synaptic mechanisms of respiratory rhythm generation

Breathing is an interesting and essential life-sustaining behavior for humans and all mammals. Like many rhythmic motor behaviors, breathing movements originate due to neural rhythms that emanate from a central pattern generator (CPG) network. CPGs produce neural-motor rhythms that often depend on specialized pacemaker neurons or alternating synaptic inhibition. But conventional models cannot explain rhythmogenesis in the respiratory preBotzinger Complex (preBotzC), the principal central pattern generator for inspiratory breathing movements, in which rhythms persist under experimental blockade of synaptic inhibition and of intrinsic pacemaker currents. Using mathematical models and experimental tests, here we demonstrate an unconventional mechanism in which metabotropic synapses and synaptic disfacilitation play key rhythmogenic roles: recurrent excitation triggers Ca2+-activated nonspecific cation current (ICAN), which initiates the inspiratory burst. Robust depolarization due to ICAN also causes voltage-dependent spike inactivation, which diminishes recurrent excitation, allowing outward currents such as Na/K ATPase pumps and K+ channels to terminate the burst and cause a transient quiescent state in the network. After a recovery period, sporadic spiking activity rekindles excitatory interactions and thus starts a new cycle. Because synaptic inputs gate postsynaptic burst-generating conductances, this rhythm-generating mechanism represents a new paradigm in which the basic rhythmogenic unit encompasses a fully inter-dependent ensemble of synaptic and intrinsic components.

3:00pm-4:30pm, WMAX 216