Learning to breathe: control of the inspiratory–expiratory phase transition shifts from sensory‐ to central‐dominated during postnatal development in rats

Abstract

The hallmark of the dynamic regulation of the transitions between inspiration and expiration is the timing of the inspiratory off-switch (IOS) mechanisms. IOS is mediated by pulmonary vagal afferent feedback (Breuer-Hering reflex) and by central interactions involving the Kölliker-Fuse nuclei (KFn). We hypothesized that the balance between these two mechanisms controlling IOS may change during postnatal development. We tested this hypothesis by comparing neural responses to repetitive rhythmic vagal stimulation, at a stimulation frequency that paces baseline breathing, using in situ perfused brainstem preparations of rats at different postnatal ages. At ages < P15 (P, postnatal days), phrenic nerve activity (PNA) was immediately paced and entrained to the afferent input and this pattern remained unchanged by repetitive stimulations, indicating that vagal input stereotypically dominated the control of IOS. In contrast, PNA entrainment at > P15 was initially insignificant, but increased after repetitive vagal stimulation or lung inflation. This progressive adaption of PNA to the pattern of the sensory input was accompanied by the emergence of anticipatory centrally mediated IOS preceding the stimulus trains. The anticipatory IOS was blocked by bilateral microinjections of NMDA receptor antagonists into the KFn and PNA was immediately paced and entrained, as it was seen at ages < P15. We conclude that as postnatal maturation advances, synaptic mechanisms involving NMDA receptors in the KFn can override the vagally evoked IOS after 'training' using repetitive stimulation trials. The anticipatory IOS may imply a hitherto undescribed form of pattern learning and recall in convergent sensory and central synaptic pathways that mediate IOS.

Increased cardio-respiratory coupling evoked by slow deep breathing can persist in normal humans

“…The breathing exercises were initiated, performed and repeated. Dutschmann et al (2009) have used this approach effectively to teach in situ rat pup preparation to breathe faster (Dutschmann et al, 2009, 2014). We expect that repeated bouts of SDB would be more effective in decreasing HR over a longer period of time than a single bout.…”

Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity

“…We also need to understand how boosting GABAergic/glycinergic NT early in development, during the critical period when Cl − currents are depolarizing and excitatory, may adversely affect mature neural circuits. It is well known that GABAergic/glycinergic inhibitory NT is important for proper phase transitions in neurons that participate in CPG circuits for both locomotion and breathing in newborn and adult animals (Daun et al, 2009; Dutschmann et al, 2009; McCrea and Rybak, 2008). Moreover, data show that GABAergic NT is involved in the brainstem response to chronic hypoxia and acute intermittent hypoxia (Chung et al, 2006; Darnall et al, 2012).…”

Encéphalites auto-immunes à anticorps antirécepteurs-NMDA, une cause fréquente d’encéphalite en réanimation

“…L'élément clé du diagnostic est la détection d'anticorps anti-R-NMDA dans le LCR [2,7,15]. Ces anticorps peuvent également être dosés dans le sang, mais c'est leur présence dans le LCR qui signe le diagnostic.…”

“…2 Physiopathologie supposée des encéphalites à anticorps anti-R-NMDA au niveau synaptique Alors qu'en condition normale (A), la libération de glutamate dans la fente synaptique induit des courants NMDA et AMPA (2-amino-3-5-methyl-3-oxo-1,2-oxazolylpropanoic acid) et ainsi une activation des neurones gabaergiques, au cours des encéphalites à anticorps anti-R-NMDA (B), la liaison des anticorps sur les récepteurs NMDA (hétéromères NR1/NR2B) va induire leur internalisation rapide entraînant une diminution des courants synaptiques induits par les R-NMDA sans modifications des courants AMPA. Cela va entraîner une inactivation des neurones gabaergiques, une dérégulation des voies excitatrices et ainsi une augmentation du glutamate extracellulaire, conduisant, d'une part, aux troubles psychotiques, à la catatonie, à la rigidité et au mutisme et provoquant, d'autre part, les mouvements anormaux stéréotypés la présence de R-NMDA sur les voies dopaminergiques, noradrénergiques et cholinergiques, alors que l'hypoventilation centrale pourrait découler de la présence de R-NMDA dans les centres respiratoires pontiques [15,29]. Ce phéno-mène d'internalisation est cependant réversible [7].…”