Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice

Abstract

The cervical sympathetic chain (CSC) innervates post-ganglionic sympathetic neurons within the ipsilateral superior cervical ganglion (SCG) of all mammalian species studied to date. The post-ganglionic neurons within the SCG project to a wide variety of structures, including the brain (parenchyma and cerebral arteries), upper airway (e.g., nasopharynx and tongue) and submandibular glands. The SCG also sends post-ganglionic fibers to the carotid body (e.g., chemosensitive glomus cells and microcirculation), however, the function of these connections are not established in the mouse. In addition, nothing is known about the functional importance of the CSC-SCG complex (including input to the carotid body) in the mouse. The objective of this study was to determine the effects of bilateral transection of the CSC on the ventilatory responses [e.g., increases in frequency of breathing (Freq), tidal volume (TV) and minute ventilation (MV)] that occur during and following exposure to a hypoxic gas challenge (10% O2 and 90% N2) in freely-moving sham-operated (SHAM) adult male C57BL6 mice, and in mice in which both CSC were transected (CSCX). Resting ventilatory parameters (19 directly recorded or calculated parameters) were similar in the SHAM and CSCX mice. There were numerous important differences in the responses of CSCX and SHAM mice to the hypoxic challenge. For example, the increases in Freq (and associated decreases in inspiratory and expiratory times, end expiratory pause, and relaxation time), and the increases in MV, expiratory drive, and expiratory flow at 50% exhaled TV (EF50) occurred more quickly in the CSCX mice than in the SHAM mice, although the overall responses were similar in both groups. Moreover, the initial and total increases in peak inspiratory flow were higher in the CSCX mice. Additionally, the overall increases in TV during the latter half of the hypoxic challenge were greater in the CSCX mice. The ventilatory responses that occurred upon return to room-air were essentially similar in the SHAM and CSCX mice. Overall, this novel data suggest that the CSC may normally provide inhibitory input to peripheral (e.g., carotid bodies) and central (e.g., brainstem) structures that are involved in the ventilatory responses to hypoxic gas challenge in C57BL6 mice.

The superior cervical ganglion is involved in chronic chemoreflex sensitization during recovery from acute lung injury

“…Four days after bilateral SCGx, the ventilatory parameters at rest remained unchanged in both Sham-operated and SCGx mice, suggesting that the input from the SCG to CB and regions of upper airway and brainstem do not tonically regulate the baseline ventilatory parameters at rest. This finding was also supported by another study from the same group where they did not find any changes in resting baseline ventilation in C57BL6 mice with transection of the cervical sympathetic chain ( Getsy et al, 2021b ). Interestingly, these studies reported that during hypoxic challenge, SCGx mice demonstrated an attenuated ventilatory response in comparison to Sham-operated mice.…”

“…This difference in response to hypoxia may be caused by multiple factors including the differences in animal species and the experimental time window post SCGx. Getsy et al (2021b) measured the hypoxic ventilatory response at 4 days post SCGx whereas we assessed chemoreflex function at 2 weeks post SCGx. It is possible that within 2 weeks the animals may develop some compensatory mechanisms through which adaptation to the acute loss of SCG-mediated chemoreflex modulation occurs.…”

Time-dependent alteration in the chemoreflex post-acute lung injury

“…The post ganglionic axons of the SCG are known to innervate the CBs ( Iturriaga et al, 2016 ). Electrical stimulation of the SCG has been shown to significantly sensitize the CB chemoreflex in hypertensive and normotensive rats ( Felippe and Paton, 2021 ; Getsy et al, 2021 ; Felippe et al, 2022 ). Therefore, an increased SCG neuronal activity during the recovery of ALI, in-part, might also contribute to chemoreflex sensitization observed in our study.…”

A Missing Voice: The Lingual Complex and Osteopathic Manual Medicine in the Context of Five Osteopathic Models

“…The lingual nerve innervates the mucous membrane of two-thirds of the anterior area of the tongue, providing somatic and gustatory sensitivity; the nerve is anastomosed in the anterior lingual area with the sensitive fibers of the facial nerve or VII cranial nerve (cord of the eardrum), providing afferent sensitive fibers [32]. Sympathetic fibers from the superior cervical ganglion reach the tongue; this connection possibly regulates the movement of the tongue based on the oxygen present and other functions not yet fully understood [33,34].…”