Highlights
- •Tonic stimulation of thoracic sympathetic chain (TSC) afferents slows respiration.
- •TSC afferents project into the thoracic spinal cord.
- •Rhythmic stimulation of TSC afferents is sufficient to entrain respiration via late-expiration.
- •The entrainment pattern suggests that TSC afferents may contribute to locomotor–respiratory coupling.
Abstract
Stimulation of thoracic sympathetic chain (TSC) afferents has been shown to slow the
respiratory rhythm in dogs, monkeys and humans. However, sparse information exists
about the physiological role of TSC afferents in modulating respiration or the central
pathways of these afferents. Here, we sought to investigate whether the perfused preparation
of juvenile rats is a suitable experimental model to study the role of TSC-afferents
in the modulation of respiration. We show that tonic (30s) TSC stimulation initially
triggered either prolonged post-inspiratory vagal nerve discharge, or when the stimulus
onset occurred in the second half of expiration, TSC stimulation also modulated late-expiratory
abdominal nerve activity. Independent of the timing of the TSC-stimulation the net
effect was lengthening of the expiratory interval and subtle shortening of inspiration.
TSC evoked respiratory modulation showed progressive habituation during the stimulus
period. Importantly, high thoracic spinal cord transections abolished the TSC-evoked
respiratory modulation, indicating that TSC afferents are likely to be relayed within
the thoracic spinal cord. Next, we repeatedly applied 400 ms trains of stimuli at
an inter-burst interval near that of the intrinsic respiratory rate and show that
rhythmic TSC stimulation has a strong potential to entrain the central respiratory
rhythm. Importantly, under the imposed rhythm, TSC stimuli became aligned with the
late expiratory phase. The entrainment pattern supports the hypothesis that the TSC
pathway may convey extra-pulmonary visceral mechano-sensory feedback that might be
sensitive to visceral mass movements during locomotion. The latter was previously
discussed to significantly contribute to the locomotor–respiratory coupling in various
mammalian species.
Keywords
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References
- Abdominal expiratory activity in the rat brainstem–spinal cord in situ: patterns, origins and implications for respiratory rhythm generation.J. Physiol. 2008; 587: 3539-3559https://doi.org/10.1113/jphysiol.2008.167502
- Breathing while trotting.Science. 1993; 262: 196-197https://doi.org/10.1126/science.8211137
- Organization of the core respiratory network: insights from optogenetic and modeling studies.PLoS Comput. Biol. 2018; 14e1006148https://doi.org/10.1371/journal.pcbi.1006148
- Ponto-medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ.J. Physiol. 2014; 592: 2605-2623https://doi.org/10.1113/jphysiol.2014.272468
- The discharge pattern recorded in chemoreceptor afferent fibres from the cat carotid body with normal circulation and during perfusion.J. Physiol. 1963; 168: 332-344https://doi.org/10.1113/jphysiol.1963.sp007195
- Abdominal muscle and diaphragm activities and cavity pressures in pressure breathing.J. Appl. Physiol. 1963; 18: 37-42https://doi.org/10.1152/jappl.1963.18.1.37
- Role of the dorsal medulla in the neurogenesis of airway protection.Pulm. Pharmacol. Ther. 2015; 35: 105-110https://doi.org/10.1016/j.pupt.2015.10.012
- Running and breathing in mammals.Science. 1983; 219: 251-256https://doi.org/10.1126/science.6849136
- Airflow synchronous with oscillatory acceleration reflects involuntary respiratory muscle activity.Respir. Physiol. Neurobiol. 2004; 140: 265-282https://doi.org/10.1016/j.resp.2004.02.007
- The variations in intra-abdominal pressure and the activity of the abdominal muscles during breathing; a study in man.J. Physiol. 1953; 122: 282-290https://doi.org/10.1113/jphysiol.1953.sp004999
- Visceral nociception: peripheral and central aspects of visceral nociceptive systems.Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 1985; 308: 325-337
- Sensory innervation of the viscera: peripheral basis of visceral pain.Physiol. Rev. 1994; 74: 95-138https://doi.org/10.1152/physrev.1994.74.1.95
- Visceral nociceptors: a new world order?.Trends Neurosci. 1992; 15: 374-378https://doi.org/10.1016/0166-2236(92)90182-8
- On the regulation of depth and rate of breathing.J. Physiol. 1972; 222: 267-295https://doi.org/10.1113/jphysiol.1972.sp009797
- Timing of medullary late-inspiratory neuron discharges: vagal afferent effects indicate possible off-switch function.J. Neurophysiol. 1993; 69: 1784-1787https://doi.org/10.1152/jn.1993.69.5.1784
- Breathing matters.Nat. Rev. Neurosci. 2018; 1https://doi.org/10.1038/s41583-018-0003-6
- Decreased Hering–Breuer input-output entrainment in a mouse model of Rett syndrome.Front. Neural Circuits. 2013; 7https://doi.org/10.3389/fncir.2013.00042
- Kölliker-Fuse nuclei regulate respiratory rhythm variability via a gain-control mechanism.Am. J. Phys. Regul. Integr. Comp. Phys. 2017; 312: R172-R188https://doi.org/10.1152/ajpregu.00238.2016
- Pontine mechanisms of respiratory control.Compr. Physiol. 2012; 2: 2443-2469https://doi.org/10.1002/cphy.c100015
- Respiratory activity in neonatal rats.Auton. Neurosci. 2000; 84: 19-29https://doi.org/10.1016/S1566-0702(00)00177-6
- Learning to breathe: control of the inspiratory–expiratory phase transition shifts from sensory- to central-dominated during postnatal development in rats.J. Physiol. 2009; 587: 4931-4948https://doi.org/10.1113/jphysiol.2009.174599
- Learning to breathe: habituation of Hering–Breuer inflation reflex emerges with postnatal brainstem maturation.Respir. Physiol. Neurobiol. 2014; 195: 44-49https://doi.org/10.1016/j.resp.2014.02.009
- Oscillation, gating, and memory in the respiratory control system.in: Comprehensive Physiology. Wiley-Blackwell, 1986: 93-114https://doi.org/10.1002/cphy.cp030203
- The effect of sympathetic stimulation on carotid nerve activity.J. Physiol. 1961; 159: 251
- Respiratory neurons mediating the Breuer–Hering reflex prolongation of expiration in rat.J. Neurosci. 1996; 16: 6526-6536https://doi.org/10.1523/JNEUROSCI.16-20-06526.1996
- Neurobiology of visceral afferent neurons: neuroanatomy, functions, organ regulations and sensations.Biol. Psychol. 1996; 42: 29-51https://doi.org/10.1016/0301-0511(95)05145-7
- Brain stem control of swallowing: neuronal network and cellular mechanisms.Physiol. Rev. 2001; 81: 929-969https://doi.org/10.1152/physrev.2001.81.2.929
- Dorsal and ventral aspects of the most caudal medullary reticular formation have differential roles in modulation and formation of the respiratory motor pattern in rat.Brain Struct. Funct. 2016; 221: 4353-4368https://doi.org/10.1007/s00429-015-1165-x
- Pulmonary afferent activity recorded from sympathetic nerves.J. Appl. Physiol. 1975; 39: 37-40
- Respiratory inhibition with sympathetic afferent stimulation in the canine and primate.J. Appl. Physiol. 1978; 44: 718-724
- Phase dynamics of coupled oscillators reconstructed from data.Phys. Rev. E. 2008; 77https://doi.org/10.1103/PhysRevE.77.066205
- Influence de la Stimulation Afférente du Nerf Splanchnique sur Les Mouvements Respiratoires chez L'Homme.Arch. Int. Physiol. 1950; 58: 90-100https://doi.org/10.3109/13813455009144941
- Central pathways of pulmonary and lower airway vagal afferents.J. Appl. Physiol. 2006; 101: 618-627https://doi.org/10.1152/japplphysiol.00252.2006
- Computational models and emergent properties of respiratory neural networks.Compr. Physiol. 2012; 2: 1619-1670https://doi.org/10.1002/cphy.c110016
- Respiratory effects of transient axial acceleration.J. Appl. Physiol. 2001; 90: 2141-2150https://doi.org/10.1152/jappl.2001.90.6.2141
- Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats.Sci. Rep. 2018; 8https://doi.org/10.1038/s41598-018-34047-w
- Brainstem mechanisms underlying the cough reflex and its regulation.Respir. Physiol. Neurobiol. 2017; 243: 60-76https://doi.org/10.1016/j.resp.2017.05.008
- Phase resetting of the respiratory cycle before and after unilateral pontine lesion in cat.J. Appl. Physiol. 1992; 72: 721-730https://doi.org/10.1152/jappl.1992.72.2.721
- Phase-dependent dynamic responses of respiratory motor activities following perturbation of the cycle in the cat.J. Physiol. 1993; 461: 321-337https://doi.org/10.1113/jphysiol.1993.sp019516
- Central modulation of pain.J. Clin. Invest. 2010; 120: 3779-3787https://doi.org/10.1172/JCI43766
- A working heart-brainstem preparation of the mouse.J. Neurosci. Methods. 1996; 65: 63-68https://doi.org/10.1016/0165-0270(95)00147-6
- Brainstem-mediated sniffing and respiratory modulation during odor stimulation.Respir. Physiol. Neurobiol. 2016; 233: 17-24https://doi.org/10.1016/j.resp.2016.07.008
- Respiratory rhythm entrainment by somatic afferent stimulation.J. Neurosci. 2005; 25: 1965-1978https://doi.org/10.1523/JNEUROSCI.3881-04.2005
- Peripheral chemoreceptors in health and disease.J. Appl. Physiol. 2004; 96: 359-366https://doi.org/10.1152/japplphysiol.00809.2003
- The dynamic basis of respiratory rhythm generation: one breath at a time.Annu. Rev. Neurosci. 2018; https://doi.org/10.1146/annurev-neuro-080317-061756
- Reflex control of diaphragm activation by thoracic afferents.J. Appl. Physiol. 1993; 75: 63-69https://doi.org/10.1152/jappl.1993.75.1.63
- Running, breathing and visceral motion in the domestic rabbit (Oryctolagus cuniculus): testing visceral displacement hypotheses.J. Exp. Biol. 1999; 202: 563-577
- Habituation and desensitization of the Hering-Breuer reflex in rat.J. Physiol. 2000; 523: 479-491https://doi.org/10.1111/j.1469-7793.2000.t01-1-00479.x
- Structural and functional architecture of respiratory networks in the mammalian brainstem.Philos. Trans.: Biol. Sci. 2009; 364: 2577-2587
- The Discharge Pattern of Single Carotid Body Chemoreceptor Units in Relation to Possible Sensory Mechanisms.Arter. Chemorecept. Blackwell Oxf., 1968: 195-204
- Central pattern generation during breathing.Trends Neurosci. 1980; 3: 275-277https://doi.org/10.1016/0166-2236(80)90100-9
- Effect of acceleration on the chest wall.J. Appl. Physiol. 1994; 76: 1242-1246https://doi.org/10.1152/jappl.1994.76.3.1242
- Quantifying interactions between real oscillators with information theory and phase models: application to cardiorespiratory coupling.Phys. Rev. E. 2013; 87https://doi.org/10.1103/PhysRevE.87.022709
- Central integration of pulmonary stretch receptor input in the control of expiration.J. Appl. Physiol. 1982; 52: 1296-1315https://doi.org/10.1152/jappl.1982.52.5.1296
Article info
Publication history
Published online: February 16, 2019
Accepted:
January 30,
2019
Received in revised form:
January 29,
2019
Received:
November 22,
2018
Identification
Copyright
© 2019 Published by Elsevier B.V.