Respiratory rhythm generation: triple oscillator hypothesis

Breathing is vital for survival but also interesting from the perspective of rhythm generation. This rhythmic behavior is generated within the brainstem and is thought to emerge through the interaction between independent oscillatory neuronal networks. In mammals, breathing is composed of three phases – inspiration, post-inspiration, and active expiration – and this article discusses the concept that each phase is generated by anatomically distinct rhythm-generating networks: the preBötzinger complex (preBötC), the post-inspiratory complex (PiCo), and the lateral parafacial nucleus (pFL), respectively. The preBötC was first discovered 25 years ago and was shown to be both necessary and sufficient for the generation of inspiration. More recently, networks have been described that are responsible for post-inspiration and active expiration. Here, we attempt to collate the current knowledge and hypotheses regarding how respiratory rhythms are generated, the role that inhibition plays, and the interactions between the medullary networks. Our considerations may have implications for rhythm generation in general.

Detailed Model of Intersegmental Coordination in the Timing Network of the Leech Heartbeat Central Pattern Generator

To address the general problem of intersegmental coordination of oscillatory neuronal networks, we have studied the leech heartbeat central pattern generator. The core of this pattern generator is a timing network that consists of two segmental oscillators, each of which comprises two identified, reciprocally inhibitory oscillator interneurons. Intersegmental coordination between the segmental oscillators is mediated by synaptic interactions between the oscillator interneurons and identified coordinating interneurons. The small number of neurons (8) and the distributed structure of the timing network have made the experimental analysis of the segmental oscillators as discrete, independent units possible. On the basis of this experimental work, we have made conductance-based models to explore how intersegmental phase and cycle period are determined. We show that although a previous simple model, which ignored many details of the living system, replicated some essential features of the living system, the incorporation of specific cellular and network properties is necessary to capture the behavior of the system seen under different experimental conditions. For example, spike frequency adaptation in the coordinating interneurons and details of asymmetries in intersegmental connectivity are necessary for replicating driving experiments in which one segmental oscillator was injected with periodic current pulses to entrain the activity of the entire network. Nevertheless, the basic mechanisms of phase and period control demonstrated here appear to be very general and could be used by other networks that produce coordinated segmental motor outflow.

Modeling Alternation to Synchrony with Inhibitory Coupling: A Neuromorphic VLSI Approach

We developed an analog very large-scale integrated system of two mutually inhibitory silicon neurons that display several different stable oscillations. For example, oscillations can be synchronous with weak inhibitory coupling and alternating with relatively strong inhibitory coupling. All oscillations observed experimentally were predicted by bifurcation analysis of a corresponding mathematical model. The synchronous oscillations do not require special synaptic properties and are apparently robust enough to survive the variability and constraints inherent in this physical system. In biological experiments with oscillatory neuronal networks, blockade of inhibitory synaptic coupling can sometimes lead to synchronous oscillations. An example of this phenomenon is the transition from alternating to synchronous bursting in the swimming central pattern generator of lamprey when synaptic inhibition is blocked by strychnine. Our results suggest a simple explanation for the observed oscillatory transitions in the lamprey central pattern generator network: that inhibitory connectivity alone is sufficient to produce the observed transition.