Computational Models and Emergent Properties of Respiratory Neural Networks

Abstract

Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered.

Novel Modeling of Work of Breathing for Its Optimization During Increased Respiratory Efforts

“…This model has been used in studies related to respiratory modeling not only by the same author [28,36,37] but also by others [38,39,40]. Recently, several studies have used its cost functions to determine the breathing pattern in subjects under assisted mechanical ventilation [39,41,42,43]. The WOB depended on model parameters whose values were not provided in any of the previous studies [9,28,36,37,38,39,40,41,42,43], which suggests that respiratory control modeling based on optimization criteria needs additional experimental and computational efforts.…”

“…Recently, several studies have used its cost functions to determine the breathing pattern in subjects under assisted mechanical ventilation [39,41,42,43]. The WOB depended on model parameters whose values were not provided in any of the previous studies [9,28,36,37,38,39,40,41,42,43], which suggests that respiratory control modeling based on optimization criteria needs additional experimental and computational efforts. In addition, two different functions were also proposed in [9] to measure the mechanical cost.…”

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

“…These circuits for breathing have remarkable adaptive and emergent properties (Devinney et al 2013;Lindsey et al 1992Lindsey et al , 2012Ramirez et al 2012) and participate in the generation of numerous other behaviors (Bartlett and Leiter 2012), including vocal communication (McLean et al 2013), coughing and swallowing, and their coordinated expression as a metabehavioral response to aspiration Shannon et al 2000). Breathing may also bind orofacial sensations (Kleinfeld et al 2014) and be involved in hippocampal processes for learning and memory (Lockmann and Belchior 2014).…”

Diving into the mammalian swamp of respiratory rhythm generation with the bullfrog

“…In mammals, on which most studies have focused, there is good evidence that the ventral respiratory column in the brainstem plays a critical role in producing the respiratory motor pattern but the functional organization within this column is still debated (McCrimmon et al, 2000;Onimaru et al, 2004). At the heart of this debate is a key question: is the rhythm generator restricted to a single brainstem kernel (i.e., a small anatomical cluster of cells), several kernels or distributed widely throughout the ventral respiratory column (Abdala et al, 2009;Lindsey et al, 2012;Smith et al, 2007)?…”