Sébastien Zanella

6 avril 2012

CRN2M, UMR 6231, CNRS - AMU, secteur Nord, Marseille

Intermittent hypoxia and NE : a bad cocktail for breathing

invité par Jean-Charles Viemari

Abstract : Episodes of hypoxia occur in a large number of pathologies such as myocardial infarcts, obstructive sleep apneas, chronic bronchitis, apneas of prematurity, Rett syndrome and sudden infant death syndrome. Therefore understanding how these bouts of hypoxia affect neuronal networks is of major importance. For instance the respiratory network is known to play a crucial role in the ventilatory response to hypoxia but might as well be affected by a lack of oxygen. This neuronal network is very dynamic and can reconfigure itself to produce adapted responses to various conditions including hypoxia. Among other mechanisms neuromodulation plays a critical role in these adaptations. Indeed neuromodulatory substances are critical for organizing networks during development, maintaining network activity and for adapting neuronal networks to changes in metabolic, behavioral and environmental conditions. Moreover, neuromodulation plays an important role in various forms of plasticity. Thus it is not surprising that disturbances in neuromodulation have been associated with many neurological conditions as well but the question is : does a change in the state of the respiratory network caused by hypoxia in several diseases affect its own response to neuromodulation ? Here I will first describe how hypoxia is detected by the body. The main mechanisms take place in well-known peripheral structures (the carotid bodies) but I will also present more controversial data on the role of the central nervous system. Then I will focus on the main results obtained during my post-doctoral training where I used a model of acute and chronic intermittent hypoxia to mimic a disease state and to study the impact of repeated bouts of hypoxia on the control of breathing. Using combined approaches from the whole animal to the single cell, I will show 1) how norepinephrine modulates the respiratory network activity under normal conditions 2) how repetitive bouts of hypoxia can change the network configuration and 3) how this reconfiguration leads to an abnormal response to neuromodulation.
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