Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms

Breathing movements in mammals are driven by rhythmic neural activity automatically generated within spatially and functionally organized brainstem neural circuits comprising the respiratory central pattern generator (CPG). This chapter reviews up-to-date experimental information and theoretical studies of the cellular and circuit mechanisms of respiratory rhythm and pattern generation operating within critical components of this CPG in the lower brainstem. Over the past several decades, there have been substantial advances in delineating the spatial architecture of essential medullary regions and their regional cellular and circuit properties required to understand rhythm and pattern generation mechanisms. A fundamental concept is that the circuits in these regions have rhythm-generating capabilities at multiple cellular and circuit organization levels. The regional cellular properties, circuit organization, and control mechanisms allow flexible expression of neural activity patterns for a repertoire of respiratory behaviors under various physiologic conditions that are dictated by requirements for homeostatic regulation and behavioral integration. Many mechanistic insights have been provided by computational modeling studies driven by experimental results and have advanced understanding in the field. These conceptual and theoretical developments are discussed.