Abstract

Preinspiratory discharge manifests in the neuronal recordings of the pre-Bötzinger complex, parafacial respiratory group, retrotrapezoid nucleus, and Kölliker-Fuse nucleus, as well as the efferent neural discharge of respiratory-related nerves innervating upper airway musculature. This neural component of triphasic eupnea contemporaneously contributes to the genesis of native and originate respiratory rhythmic activity, as well as the preinspiratory component of efferent neural respiratory discharges. In the course of our investigations evaluating hypoglossal discharge in response to asphyxia, we noted a curious pattern of neural respiratory recovery following postasphyxia resuscitation in hypoglossal, vagal, and phrenic neurograms in unanesthetized decerebrate rats. Specifically, we observed a gradual return of a pseudobiphasic eupnea characterized by initial transition bursts followed by robust eupneic bursts with dynamics inclusive of a gradually and progressively increasing duration of the hypoglossal eupneic bursts and duration and amplitude of the preinspiratory component of these bursts, as well as progressively lengthening expiratory interval between these bursts in the phrenic nerve discharge. This was followed by conversion to regular triphasic eupnea. We discuss our extrapolations based on these findings regarding eupneic respiratory central pattern generation and mechanisms contributing to the genesis of preinspiratory activity in hypoglossal discharge.

Highlights

  • Triphasic eupnea consists of inspiratory, postinspiratory, and late expiratory neural respiratory activities (Marchenko et al, 2016; Richter, 1982; Richter et al, 1986; Smith et al, 2007), generated by the interaction of rhythm generating circuitry located within the Bötzinger and pre-Bötzinger complexes with elements in the dorsolateral metencephalon, including Kölliker-Fuse and medial parabrachial nuclei (Dutschmann and Herbert, 2006; Molkov et al, 2017; Mörschel and Dutschmann, 2009), thence relayed to the pattern generating elements of the rostral and caudal divisions of the ventral respiratory group (Figs. 1 and 2) (Anderson and Ramirez, 2017; Bonis et al, 2010a,b; Cui et al, 2016; Ramirez and Baertsch, 2018; Richter and Smith, 2014; Smith et al, 1991, 2007)

  • Preinspiratory discharge occurs during the late expiratory phase and immediately precedes and drives inspiratory onset (Fortuna et al, 2008; Fregosi and Fuller, 1997; Ghali, 2015; Ghali and Marchenko, 2016; Lee et al, 2003, 2006, 2007a,b, 2008, 2012; Lee and Fuller, 2010a,b; Lee and Pisarri, 2001; Leiter and St-John, 2004; Molkov et al, 2017), evident in the neuronal recordings of the pre-Bötzinger complex (Malheiros-Lima et al, 2018; Marchenko et al, 2016) and parafacial respiratory group intrinsic bursting cells (Onimaru et al, 2008), Kölliker-Fuse nucleus (Kobayashi et al, 2005), as well as the efferent neural discharge of hypoglossal, vagal, and upper airway related nerve activity (Ghali, 2015; Ghali and Marchenko, 2016; Lee and Fuller, 2010a)

  • We present evidence demonstrating the gradual recovery of neural respiratory discharge in the hypoglossal, vagal, and phrenic motor outputs reflect gradual recovery of inhibitory network elements in ventral respiratory column nuclei in response to asphyxia in the unanesthetized decerebrate preparation of the adult rat (Fig. 6)

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Summary

Introduction

Triphasic eupnea consists of inspiratory, postinspiratory, and late expiratory neural respiratory activities (Marchenko et al, 2016; Richter, 1982; Richter et al, 1986; Smith et al, 2007), generated by the interaction of rhythm generating circuitry located within the Bötzinger and pre-Bötzinger complexes with elements in the dorsolateral metencephalon, including Kölliker-Fuse and medial parabrachial nuclei (Dutschmann and Herbert, 2006; Molkov et al, 2017; Mörschel and Dutschmann, 2009), thence relayed to the pattern generating elements of the rostral and caudal divisions of the ventral respiratory group (Figs. 1 and 2) (Anderson and Ramirez, 2017; Bonis et al, 2010a,b; Cui et al, 2016; Ramirez and Baertsch, 2018; Richter and Smith, 2014; Smith et al, 1991, 2007). Preinspiratory discharge occurs during the late expiratory phase and immediately precedes and drives inspiratory onset (Fortuna et al, 2008; Fregosi and Fuller, 1997; Ghali, 2015; Ghali and Marchenko, 2016; Lee et al, 2003, 2006, 2007a,b, 2008, 2012; Lee and Fuller, 2010a,b; Lee and Pisarri, 2001; Leiter and St-John, 2004; Molkov et al, 2017), evident in the neuronal recordings of the pre-Bötzinger complex (Malheiros-Lima et al, 2018; Marchenko et al, 2016) and parafacial respiratory group intrinsic bursting cells (Onimaru et al, 2008), Kölliker-Fuse nucleus (Kobayashi et al, 2005), as well as the efferent neural discharge of hypoglossal, vagal, and upper airway related nerve activity (Ghali, 2015; Ghali and Marchenko, 2016; Lee and Fuller, 2010a). We discuss several alternative hypotheses that could exist to explain these observations and present our conjectures

Respiratory rhythm generation and pattern formation
Hypoglossal discharge
Genesis nuclei for preinspiratory discharge in hypoglossal motoneurons
Pseudobiphasic postresuscitative neural respiratory discharge
Clinical Relevance
Conclusions
Ethical approval
Full Text
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