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

Abstract

Key points Dysfunctions in the hypoglossal control of tongue extrinsic muscles are implicated in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH), an important feature of OSA syndrome, produces deleterious effects on the motor control of oropharyngeal resistance, but whether the hypoglossal motoneurones innervating the tongue extrinsic muscles are affected by CIH is unknown. We show that CIH enhanced the respiratory‐related activity of rat hypoglossal nerve innervating the protrudor and retractor tongue extrinsic muscles. Intracellular recordings revealed increases in respiratory‐related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones after CIH. CIH also increased their intrinsic excitability, depolarised resting membrane potential and reduced K+‐dominated leak conductance. CIH affected the breathing‐related synaptic control and intrinsic electrophysiological properties of protrudor and retractor hypoglossal motoneurones to optimise the neural control of oropharyngeal function. Abstract Inspiratory‐related tongue movements and oropharyngeal motor actions are controlled mainly by the protrudor and retractor extrinsic tongue muscles, which are innervated by the hypoglossal motoneurones. Chronic intermittent hypoxia (CIH), an important feature of obstructive sleep apnoea syndrome, produces detrimental effects on the contractile function of the tongue extrinsic muscles and the medullary inspiratory network of rodents. However, the impact of the CIH on the electrophysiological properties of protrudor and retractor hypoglossal motoneurones has not been described before. Using nerves and intracellular recordings in in situ preparation of rats (5 weeks old), we tested the hypothesis that CIH (FiO2 of 0.06, SaO2 74%, during 30–40 s, every 9 min, 8 h/day for 10 days) increases the intrinsic excitability of protrudor and retractor motoneurones from the hypoglossal motor nucleus of rats. Recordings of hypoglossal nerve, before its bifurcation to innervate the tongue protrudor and retractor muscles, revealed that CIH enhances its pre‐inspiratory, simultaneously with the presence of active expiration, and inspiratory activities. These changes were mediated by increases in the respiratory‐related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones. Besides, CIH increases their intrinsic excitability and depolarises resting membrane potential by reducing a K+‐dominated leak conductance. In conclusion, CIH enhances the respiratory‐related neural control of oropharyngeal function of rats by increasing the synaptic excitation, intrinsic excitability, and reducing leak conductance in both protrudor and retractor hypoglossal motoneurones. We propose that these network and cellular changes are important to optimise the oropharyngeal resistance in conditions related to intermittent hypoxia.

Lactate ions induce synaptic plasticity to enhance output from the central respiratory network

“…Given the conservation of the cellular mechanisms for synaptic plasticity mechanisms across vertebrates, lactate signalling has the potential to influence the central respiratory network in mammals. Rats exposed to chronic intermittent hypoxia have enhanced excitatory synaptic drive onto hypoglossal motoneurons (da Silva et al 2021) and exhibit greater phrenic motor plasticity that relies on flux through glycolysis (MacFarlane et al 2018). Both examples are consistent with a potential role for lactate-induced respiratory motor plasticity in mammals as well as amphibians.…”

“…Rats exposed to chronic intermittent hypoxia have enhanced excitatory synaptic drive onto hypoglossal motoneurons (da Silva et al . 2021) and exhibit greater phrenic motor plasticity that relies on flux through glycolysis (MacFarlane et al . 2018).…”

Kidney Renin Release under Hypoxia and Its Potential Link with Nitric Oxide: A Narrative Review

“…Intermittent hypoxia is composed of hypoxia-normoxia cycles. Hypoxia-normoxia cycles are controlled by individually ventilated cages, which can rapidly change the fraction of inspired oxygen (FiO 2 ) in seconds [29]. In Fletcher's research, the hypoxia-normoxia cycle was 2 min per cycle and the lowest FiO 2 level reached 2% or 3%.…”

Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

“…CIH and the increased gain in carotid body activity lead to disturbances in multiple neuronal mechanisms originating in the central nervous system ( Arias-Cavieres et al, 2021 ; Arias-Cavieres et al, 2020 ; da Silva et al, 2021 ; Domingos-Souza et al, 2021 ; Jia et al, 2022 ; Kline, 2010 ; Kline et al, 2019 ; Lin et al, 2007 ; Marciante et al, 2021 ; Ramirez et al, 2020 ; Souza et al, 2019 ). CIH directly affects neuronal network functions within the ventral respiratory column (VRC), in particular the preBötzinger complex (preBötC) ( Garcia et al, 2017 ; Garcia et al, 2016 ), a critical rhythmogenic network implicated in swallow-breathing coordination ( Huff et al, 2022 ).…”