Retracted: Control of hypoglossal pre‐inspiratory discharge

Abstract

The hypoglossal nerve (XII) innervates muscles mediating excursive movements of the tongue. The population discharge of hypoglossalmotoneuronal axons constituting the hypoglossal nerve precedes and extends through the inspiratory epoch. The epoch subtended between the onsets of hypoglossal and phrenic neural discharge constitutes so-called pre-inspiration. Hypoglossal pre-inspiratory neural discharge serendipitously displaces the tongue along a tensor reducing upper airway resistance anticipative of succeeding inspiratory efforts. Hypoglossal motoneurons exhibiting discharge onset during pre-inspiration experience successive hyperpolarization of membrane voltage and attenuation of unitary spiking frequency, although a subset may, paradoxically and state-dependently, exhibit depolarization of membrane voltage and augmentation of neuronal spiking frequency, by dynamic stretch placed upon the alveolar walls and interstitium. Marked static elevation of positive-end expiratory pressure may induce hypoglossal bursting decoupled from phasic rhythmic phrenic discharge. Augmentation of the amplitude and/or duration of hypoglossal inspiratory discharge during successive pre-inspiratory and inspiratory epochs by inhalation of a hypoxic and/or hypercapnic gas mixture remains restrained in the presence of intact vagal inputs and is potentiated by interruptions of vagal continuity. Unravelling the mechanisms underlying the genesis of pre-inspiratory activity will inform our understanding of respiratory rhythm generation and pattern shaping. In the present work, I seek to explore the mechanisms underlying modulation of hypoglossal pre-inspiratory discharge by hypercapnia, hypoxia and static and dynamic lung stretch placed upon hypoglossal pre-inspiratory activity, the mechanisms underlying the generation of hypoglossal pre-inspiratory activity, and the extent of microanatomical and functional overlap between propriobulbar interneuronal microcircuits generating hypoglossal pre-inspiratory activity and propriobulbar interneuronal microcircuit oscillators generating pre-inspiratory activity inaugurally inducing respiratory rhythmic activity and thus use experimental data from previous work and that developed by other investigators to explore the modulatory role of lung vagal afferents and intra-neuraxial and carotid body chemoreceptors upon hypoglossal pre-inspiratory activity.

Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones

“…It was demonstrated that protrudor and retractor muscle co-activation, such as during acute hypoxia (Fuller et al 1998), produces tongue retraction during inspiration and improves oropharyngeal flow in rats (Eisele et al 1995;Brennick et al 2001). Our working hypothesis is that the enhancement of the tongue extrinsic muscle activity immediately before (simultaneously with glottal dilatation and active expiration (Moraes & Machado, 2015)) and during inspiration in rats submitted to CIH produces maximal expiratory and inspiratory flow, reducing the resistance of the oropharyngeal and laryngeal airways (Fuller et al 1999;Bailey & Fregosi, 2003;Ghali, 2020). Accordingly, hypoxic episodes reduce upper airway airflow resistance in rats and humans (Shkoukani et al 2002;Fuller, 2005).…”

“…Our working hypothesis is that the enhancement of the tongue extrinsic muscle activity immediately before (simultaneously with glottal dilatation and active expiration (Moraes & Machado, 2015)) and during inspiration in rats submitted to CIH produces maximal expiratory and inspiratory flow, reducing the resistance of the oropharyngeal and laryngeal airways (Fuller et al . 1999; Bailey & Fregosi, 2003; Ghali, 2020). Accordingly, hypoxic episodes reduce upper airway airflow resistance in rats and humans (Shkoukani et al .…”