Brainstem respiratory networks: building blocks and microcircuits

Abstract

Breathing movements in mammals are driven by rhythmic neural activity generated within spatially and functionally organized brainstem neural circuits comprising the respiratory central pattern generator (CPG). This rhythmic activity provides homeostatic regulation of gases in blood and tissues and integrates breathing with other motor acts. We review new insights into the spatial–functional organization of key neural microcircuits of this CPG from recent multidisciplinary experimental and computational studies. The emerging view is that the microcircuit organization within the CPG allows the generation of multiple rhythmic breathing patterns and adaptive switching between them, depending on physiological or pathophysiological conditions. These insights open the possibility for site- and mechanism-specific interventions to treat various disorders of the neural control of breathing.

Neural mechanisms underlying respiratory rhythm generation in the lamprey

“…the hypothesized rostral expiratory oscillator of mammals (see e.g. Onimaru et al, 2009;Thoby-Brisson et al, 2009;Guyenet and Mulkey, 2010;Feldman et al, 2013;Smith et al, 2013). This oscillator may display burst activity involving endogenous I NaP -dependent properties, as it occurs in the preBötC ThobyBrisson et al, 2009;Molkov et al, 2010).…”

“…The primordial respiratory trigeminal oscillator capable of generating a very simple respiratory pattern is progressively embedded into a complex distributed neural network subserving the generation of the breathing pattern in mammals (Smith et al, 2007(Smith et al, , 2013. We believe that the main concern in the evolution of the neural control of breathing is not represented by the complexity of the breathing pattern that can be fairly complex also in lower vertebrates, but by other properties of respiration, such as rhythm stabilization, optimization of the energetic cost, integration with other non respiratory functions of respiratory muscles and adjustments to different behavioral and environmental conditions (Von Euler, 1986).…”

AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea

“…Ventilatory movements are delivered by respiratory central pattern generators (rCPGs) distributed bilaterally in the pons and ventral medulla. These semiautonomous neural networks comprise core circuits of excitatory and inhibitory interneurons that deliver rhythmic patterns of activity (10) and confer a set point about which respiratory rhythm is continuously modulated through the integration of inputs from those central (10,11) and peripheral (12) chemosensors that monitor O 2 , CO 2 , and pH. It is generally accepted that the carotid bodies represent the primary arterial chemoreceptors (12) and that the acute hypoxic ventilatory response (HVR) is delivered by increased afferent discharge from the carotid bodies to the rCPGs via, in great part, catecholaminergic networks within the caudal brainstem (13,14).…”

Neurônios catecolaminérgicos do tronco encefálico participam dos ajustes respiratórios induzidos por hipóxia e hipercapnia.

“…O VLM é subdividido em três porções: rostral, intermediária e caudal, sendo, respectivamente, denominadas de bulbo ventrolateral rostral (RVLM), bulbo ventrolateral intermediário (IVLM) e bulbo ventrolateral caudal (CVLM). Nestas regiões, estão localizados diversos grupamentos neuronais envolvidos no controle cardiovascular e respiratório (Spyer, Gourine, 2009;Smith et al, 2013 …”