Response of respiratory-related hypoglossal nerve activity to capsaicin-induced pulmonary C-fiber activation in rats

Retracted: Control of hypoglossal pre‐inspiratory discharge

“…These effects of i.v . administration of capsaicin upon breathing are consistent with Bezold–Jarisch reflex‐related apnoea, suggesting that late‐recruited high‐threshold medullary lateral tegmental field units modulate propriobulbar interneuronal microcircuit oscillators constituting the respiratory rhythm generator (Lee et al., 2003, 2007b, 2008, 2012). These differential effects upon heterologous motor outputs might be explained by intrajugular administration of capsaicin recruiting distinct sets of neural circuits alternately promoting or attenuating inspiratory‐related discharge in hypoglossal neural efferent activity in parallel.…”

“…Intratracheal administration of a hypercapnic gas mixture fails to augment pre‐inspiratory activity in hypoglossal neural efferent discharge in the presence of vagal continuity in unanaesthetized decerebrated rats (Ghali & Marchenko, 2016a) and insufficiently overcomes inhibitory modulation of pre‐inspiratory activity in hypoglossal neural efferent discharge promoted by i.v . administration of capsaicin (see Lee et al., 2003). Abrogation of stimulation of pre‐inspiratory activity in hypoglossal neural efferent discharge corroborates the presumptive conjecture that unmyelinated C fibres within the vagus nerve exhibiting continuous tonic discharge might contribute to presynaptically gatingly restricting the distribution of pre‐inspiratory activity to hypoglossal motoneurons, attenuate distinct subsets of premotoneurons axodendritically and axosomatically conferring pre‐inspiratory discharge upon hypoglossal motoneurons, or inhibit distinct subsets of hypoglossal motoneurons exhibiting pre‐inspiratory inspiratory phase‐spanning discharge in preparations preserving vagal continuity (Ghali & Marchenko, 2016a).…”

“…Electron microscopic evaluation of neurons residing within the ventrolateral division of the NTS to identify the organization and differential prevalence of Golgi type I and II synapses will permit us to develop a more intimate and nuanced appreciation of the functional heterogeneity and stereotypic modulation of respiratory rhythm generation and pattern formation by dynamic pulmonary stretch (Izzo, Sykes, & Spyer, 1992). Tonically discharging vagal C fibres putatively exerting an inhibitory influence upon pre‐inspiratory activity might synergistically contribute cross‐modally to this functional segregation of hypoglossal motoneurons from the influences of the preBötzC and subject them to unhindered monosynaptic and polysynaptic modulation by distinct sets of propriobulbar interneuronal pre‐I oscillators residing within the lateral zones of the parafacial respiratory group (Lee et al., 2003). Concurrent excitation of late‐expiratory discharge and attenuation of late‐inspiratory discharge by dynamic pulmonary stretch mighty thus conspire to successively attenuate pre‐inspiratory discharge in hypoglossal neural efferent activity and idiosyncratically and suddenly elicit phrenic‐decoupled hypoglossal bursting (Ghali & Marchenko, 2016a).…”

“…administration of phenylbiguanide coordinately elicited depolarization of the membrane voltage of decrementing post‐inspiratory neurons and attenuated discharge by inspiratory‐related neurons, but failed to abolish the rhythmic firing exhibited by pre‐inspiratory neurons within the preBötzC, revealed by individual intracellular unit recordings conducted in situ and in vivo in mice (Paton, 1997). Administration of capsaicin, presumably selectively enhancing the discharge of unmyelinated vagal C fibres, attenuates pre‐inspiratory activity in hypoglossal neural efferent discharge (Lee et al., 2003, 2007b), but fails to modify appreciably the pre‐inspiratory activity of preBötzC propriobulbar interneurons (Paton, 1997). Thus, pre‐inspiratory activity generated by neurons within the preBötzC cannot be the source of pre‐inspiratory activity manifesting within hypoglossal neural efferent discharge heterosynaptically modulated by the activation of vagal C fibres, indicating that the chief source of pre‐I activity manifesting in hypoglossal neural efferent discharge must be distinct from the preBötzC.…”

Capsaicin causes robust reduction in glycinergic transmission to rat hypoglossal motor neurons via a TRPV1-independent mechanism

“…Capsaicin potently inhibits the respiratory central pattern generator in the in vitro rhythmically active brainstem/spinal cord preparation and in vivo plethysmographic recordings via TRPV1 receptors, eliciting tonic hypoglossal motor activity in parallel with respiratory apnea (Ren et al 2017). Capsaicin also elicited hypoglossal nerve activity in an in vivo study in anaesthetized rats (Lee et al 2003). Although capsaicin has been classically considered as a selective TRPV1 agonist, we have shown that it causes a non-TRPV1-mediated reduction in inhibitory glycinergic transmission to XII MNs.…”