Advances in cellular and integrative control of oxygen homeostasis within the central nervous system

Abstract

Mammals must continuously regulate the levels of O and CO , which is particularly important for the brain. Failure to maintain adequate O /CO homeostasis has been associated with numerous disorders including sleep apnoea, Rett syndrome and sudden infant death syndrome. But, O /CO homeostasis poses major regulatory challenges, even in the healthy brain. Neuronal activities change in a differentiated, spatially and temporally complex manner, which is reflected in equally complex changes in O demand. This raises important questions: is oxygen sensing an emergent property, locally generated within all active neuronal networks, and/or the property of specialized O -sensitive CNS regions? Increasing evidence suggests that the regulation of the brain's redox state involves properties that are intrinsic to many networks, but that specialized regions in the brainstem orchestrate the integrated control of respiratory and cardiovascular functions. Although the levels of O in arterial blood and the CNS are very different, neuro-glial interactions and purinergic signalling are critical for both peripheral and CNS chemosensation. Indeed, the specificity of neuroglial interactions seems to determine the differential responses to O , CO and the changes in pH.

The logic behind neural control of breathing pattern

“…We refer to the periods of the control inputs as “low”, “medium” or “large” when, if acted on their respected isolated population, they result in tonic spiking, bursting or silence respectively (the actual values will depend on the size of the memory and threshold in each population). The transition from 3- to 2- to 1- phase pattern seen in our model is consistent with reducing energy due, for example, to lack of oxygen 6,14,27 . The system is also capable of displaying tonic spiking if the period of is low and the periods of and are high (not shown in the figure) and silence if the period of is low or if the periods of , and are all high.

Figure 3Transition from 3- to 2- to 1-phase pattern in the larger network (Fig.

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Advances in cellular and integrative control of oxygen and carbon dioxide homeostasis

“…The review by Guyenet et al (2018) discusses the functionally important interactions that occur between the carotid bodies and the central CO 2 -sensitive neurons in the retrotrapezoid nucleus in the control of breathing in various conditions. Ramirez et al (2018) extend this discussion with insights into central neural mechanisms of oxygen sensing and homeostasis and the emergent role of central astrocytes as differential modulators of central chemosensory networks.…”

“…Ramirez et al . () extend this discussion with insights into central neural mechanisms of oxygen sensing and homeostasis and the emergent role of central astrocytes as differential modulators of central chemosensory networks.…”

Purinergic signaling mediates neuroglial interactions to generate sighs

“…Astrocytes respond to metabolic changes in their extracellular environment by increasing intracellular Ca 2+ 20 through G-protein coupled receptor cascades. In the respiratory networks 21,22 , and throughout the central nervous system 23,24 , astrocyte responses spread through gap junctions 25 and involve the release of ATP which modulates neural activity via purinergic mechanisms [26][27][28] . Therefore, we tested the contribution of purinergic signaling to sigh generation in vitro by pharmacological manipulation of ADP and ATP receptors P2Y1 and P2X, respectively (Fig.…”