The lamprey respiratory network: Some evolutionary aspects

https://doi.org/10.1016/j.resp.2021.103766Get rights and content

Highlights

  • The lamprey respiratory rhythm generator is located in the paratrigeminal respiratory group (pTRG).

  • The pTRG displays similarities with the mammalian preBötzinger complex.

  • Both excitatory and inhibitory amino acids have important roles in respiratory rhythm generation.

  • Extensive neuromodulation of the pTRG is exerted by SP, ACh, 5-HT, purinergic signalling and astrocytes.

  • Some important characteristics of the respiratory rhythm generator are highly maintained throughout evolution.

Abstract

Breathing is a complex behaviour that involves rhythm generating networks. In this review, we examine the main characteristics of respiratory rhythm generation in vertebrates and, in particular, we describe the main results of our studies on the role of neural mechanisms involved in the neuromodulation of the lamprey respiration. The lamprey respiratory rhythm generator is located in the paratrigeminal respiratory group (pTRG) and shows similarities with the mammalian preBötzinger complex. In fact, within the pTRG a major role is played by glutamate, but also GABA and glycine display important contributions. In addition, neuromodulatory influences are exerted by opioids, substance P, acetylcholine and serotonin. Both structures respond to exogenous ATP with a biphasic response and astrocytes there located strongly contribute to the modulation of the respiratory pattern. The results emphasize that some important characteristics of the respiratory rhythm generating network are, to a great extent, maintained throughout evolution.

Introduction

Breathing is a complex behaviour that requires sophisticated control mechanisms enabling animals to respond properly to physiological challenges and changing environmental conditions. Like locomotion and other rhythmic behaviours for which the motor pattern is generated within the brainstem and/or spinal cord without the need for peripheral or suprapontine inputs, breathing originates from a central rhythmogenic circuit. It is well known that there are similarities in the topography and functional characteristics between groups of respiration-related neurons in the hindbrain of different vertebrate groups (see e.g. Taylor et al., 1999, 2010). Therefore, a comparative approach among vertebrates may provide important insights into how multiple rhythmic circuits become functionally intertwined to produce and coordinate respiratory behaviours. There are also important differences related to the specific modes of vertebrates’ respiration. Fish typically propel water in a unidirectional fashion over the gills using ventilatory muscles operating around the jaws, the branchial muscles and the opercular muscles in teleosts. In the amphibian tadpole larvae ventilation is maintained by the activity of cranial muscles, while in the adult amphibians a buccal force pump contributes to both gill and lung breathing. Reptiles are the first group of vertebrates to use a thoracic aspiration pump to ventilate the lungs. Although they typically lack a diaphragm per se, the presence of the diaphragmaticus muscle contributes to creating the negative pressure necessary for lung ventilation. In mammals, lung ventilation is realized through coordinate contractions of diaphragmatic, intercostal and/or abdominal muscles along with some accessory respiratory muscles. The respiratory system in birds resembles that of mammals, but they lack a diaphragm and their lungs are ventilated by volume changes in the air sacs.

In the present review, we examine the main characteristics of the control of breathing in vertebrates and, in particular, we describe the main results of our studies concerning neural mechanisms involved in respiratory rhythm generation and its modulation within the lamprey respiratory network. The lamprey central nervous system may represent an ideal model to provide insights into the basic neural mechanisms of rhythmic activities, such as locomotion and respiration, owing to the presence of fewer neurons than in higher vertebrates and the experimental advantage that it can be maintained in vitro along with spontaneous respiratory activity (Grillner, 2003, 2006).

Section snippets

A few notes on evolutionary aspects of vertebrate respiration

The mammalian breathing rhythm arises from the preBötzinger complex (preBötC), a medullary neural network essential for normal breathing and widely recognized as necessary and sufficient to generate the inspiratory phase of respiration (Smith et al., 1991; for reviews see Feldman et al., 2013; Del Negro et al., 2018). This region has been identified in several mammal species, including goats, cats, rabbits, rats, mice and humans (Smith et al., 1991; Schwarzacher et al., 1995, 2011; Ramirez et

Characterization of the lamprey pTRG

Breathing in the adult lamprey is produced by synchronous contractions of the branchial muscles that pump water in and out of gill pores. Exhalation is the only active process produced by muscle contractions which compress the branchial basket, while inhalation is passive and occurs when the branchial basket expands by passive recoil during muscle relaxation, drawing fresh water back into the sacs (Rovainen, 1977, 1979). The respiratory motoneurons are located in three distinct motor nuclei,

General features

The crucial role of the pTRG in lamprey respiratory rhythm generation recalls that attributed to the mammalian preBötC (see e.g. Smith et al., 1991; Bongianni et al., 2016; Cinelli et al., 2017; Del Negro et al., 2018; Ramirez and Baertsch, 2018). The two rhythm generators exhibit many similarities. Excitatory and inhibitory amino acids have a prominent role in both neural networks that are under extensive neuromodulatory control and display sensitivity to opioids, substance P (SP),

Final considerations

Attempts to draw homologies between the central respiratory rhythm generator of the lamprey and that of mammals could appear speculative since the muscles and pumps used to ventilate the respiratory system are completely different, i.e. a buccal/branchial force pump in lampreys versus an aspiration pump in mammals. However, similarly to other neurophysiological features (see e.g. Grillner and El Manira, 2020), some prominent similarities between the pTRG and the preBötC indicate that the main

Authors contributions

All Authors prepared figures, drafted manuscript, edited and revised manuscript and approved final version of the manuscript.

Acknowledgements

This study was supported by grants from the University of Florence and from the Ente Cassa di Risparmio Firenze, Italy.

References (160)

  • Y. Cui et al.

    Defining preBötzinger complex rhythm- and pattern-generating neural microcircuits in vivo

    Neuron

    (2016)
  • A. Doi et al.

    Neuromodulation and the orchestration of the respiratory rhythm

    Respir. Physiol. Neurobiol.

    (2008)
  • M.A. Douse et al.

    Episodic respiratory related discharge in turtle cranial motoneurons: in vivo and in vitro studies

    Brain Res.

    (1990)
  • M.A. Douse et al.

    Episodic breathing in alligators: role of sensory feedback

    Respir. Physiol.

    (1992)
  • J.S. Erlichman et al.

    ATP, glia and central respiratory control

    Respir. Physiol. Neurobiol.

    (2010)
  • G.D. Funk et al.

    Neuroglia and their roles in central respiratory control; an overview

    Comp. Biochem. Physiol. A Mol. Integr. Physiol.

    (2015)
  • S. Grillner

    Biological pattern generation: the cellular and computational logic of networks in motion

    Neuron

    (2006)
  • J.C. Guimond et al.

    Anatomical and physiological study of respiratory motor innervation in lampreys

    Neuroscience

    (2003)
  • G. Hilaire et al.

    The role of serotonin in respiratory function and dysfunction

    Respir. Physiol. Neurobiol.

    (2010)
  • M.R. Hodges et al.

    Contributions of 5-HT neurons to respiratory control: neuromodulatory and trophic effects

    Respir. Physiol. Neurobiol.

    (2008)
  • M. Hoffman et al.

    Evolution of lung breathing from a lungless primitive vertebrate

    Respir. Physiol. Neurobiol.

    (2016)
  • L. Iovino et al.

    Breathing stimulation mediated by 5-HT1A and 5-HT3 receptors within the preBötzinger complex of the adult rabbit

    Brain Res.

    (2019)
  • T.A. Janes et al.

    Development of central respiratory control in anurans: the role of neurochemicals in the emergence of air-breathing and the hypoxic response

    Respir. Physiol. Neurobiol.

    (2019)
  • S.M. Johnson et al.

    Respiratory neuron characterization reveals intrinsic bursting properties in isolated adult turtle brainstems (Trachemys scripta)

    Respir. Physiol. Neurobiol.

    (2016)
  • R. Kinkead

    Phylogenetic trends in respiratory rhythmogenesis: insights from ectothermic vertebrates

    Respir. Physiol. Neurobiol.

    (2009)
  • B. Martel et al.

    Respiratory rhythms generated in the lamprey rhombencephalon

    Neuroscience

    (2007)
  • J.-C. Martel et al.

    WAY-100635 has high selectivity for serotonin 5-HT1A versus dopamine D4 receptors

    Eur. J. Pharmacol.

    (2007)
  • W.K. Milsom

    Central control of air breathing in fishes

    Acta Histochem.

    (2018)
  • K. Missaghi et al.

    The neural control of respiration in lampreys

    Respir. Physiol. Neurobiol.

    (2016)
  • D. Mutolo

    Brainstem mechanisms underlying the cough reflex and its regulation

    Respir. Physiol. Neurobiol.

    (2017)
  • D. Mutolo et al.

    Opioid-induced depression in the lamprey respiratory network

    Neuroscience

    (2007)
  • S.B. Abbott et al.

    Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats

    J. Neurosci.

    (2011)
  • A.P. Abdala et al.

    Abdominal expiratory activity in the rat brainstem-spinal cord in situ: patterns, origins and implications for respiratory rhythm generation

    J. Physiol.

    (2009)
  • T.M. Anderson et al.

    Respiratory rhythm generation: triple oscillator hypothesis

    F1000Res.

    (2017)
  • T.M. Anderson et al.

    A novel excitatory network for the control of breathing

    Nature

    (2016)
  • M. Antri et al.

    Ontogeny of 5-HT neurons in the brainstem of the lamprey, Petromyzon marinus

    J. Comp. Neurol.

    (2006)
  • S. Ashhad et al.

    Emergent elements of inspiratory rhythmogenesis: network synchronization and synchrony propagation

    Neuron

    (2020)
  • M.I. Baghdadwala et al.

    Three brainstem areas involved in respiratory rhythm generation in bullfrogs

    J. Physiol.

    (2015)
  • F. Bongianni et al.

    Group I and II metabotropic glutamate receptors modulate respiratory activity in the lamprey

    Eur. J. Neurosci.

    (2002)
  • F. Bongianni et al.

    Neurokinin receptor modulation of respiratory activity in the rabbit

    Eur. J. Neurosci.

    (2008)
  • P. Bouverot

    Control of breathing in birds compared with mammals

    Physiol. Rev.

    (1978)
  • B.R. Chemel et al.

    WAY-100635 is a potent dopamine D4 receptor agonist

    Psychopharmacology (Berl.)

    (2006)
  • E. Cinelli et al.

    Neuronal mechanisms of respiratory pattern generation are evolutionary conserved

    J. Neurosci.

    (2013)
  • E. Cinelli et al.

    GABAergic and glycinergic inputs modulate rhythmogenic mechanisms in the lamprey respiratory network

    J. Physiol.

    (2014)
  • E. Cinelli et al.

    ATP and astrocytes play a prominent role in the control of the respiratory pattern generator in the lamprey

    J. Physiol.

    (2017)
  • E. Cinelli et al.

    Key role of 5-HT1A receptors in the modulation of the neuronal network underlying the respiratory rhythm generation in lampreys

    Eur. J. Neurosci.

    (2020)
  • A.E. Corcoran et al.

    Dual effects of 5-HT(1a) receptor activation on breathing in neonatal mice

    J. Neurosci.

    (2014)
  • C. Davidson et al.

    (+)-WAY 100135, a partial agonist, at native and recombinant 5-HT1B/1D receptors

    Br. J. Pharmacol.

    (1997)
  • C.A. Del Negro et al.

    Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation

    J. Neurosci.

    (2005)
  • C.A. Del Negro et al.

    Breathing matters

    Nat. Rev. Neurosci.

    (2018)
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