Research ReportGABAergic and glycinergic inhibitory mechanisms in the lamprey respiratory control
Introduction
The neural mechanisms involved in respiratory rhythm generation have been investigated mainly in mammals (Ezure, 2004, Feldman et al., 2003); however, several issues still remain to be resolved. Further insights into the mechanisms underlying the genesis of rhythmic activities may arise from studies on lower vertebrates, such as the lamprey (see, e.g., Grillner, 2003, Marder and Calabrese, 1996). In the adult lamprey, breathing is produced by synchronous contractions of the branchial muscles that force water out of the gill openings. The subsequent refilling of the gill sacs is produced by the elastic recoil of the cartilaginous gill baskets surrounding them (Rovainen, 1977). The isolated brain spontaneously produces respiratory neuronal activity in vitro; this activity closely resembles that underlying the respiratory behaviour of intact animals and persists after transections of the brain at the obex and isthmus levels (e.g., Bongianni et al., 1999, Bongianni et al., 2002, Rovainen, 1977, Rovainen, 1983, Russell, 1986, Thompson, 1985). Thus, both the neural network responsible for respiratory rhythm generation and respiratory motoneurons are located within the brainstem. Little is known as regards the neural mechanisms underlying respiratory rhythmogenesis in the lamprey. Respiratory motoneurons are situated in the facial, glossopharyngeal and, especially, in the vagal nuclei, but the respiratory central pattern generator (CPG) has not yet been clearly identified (e.g., Bongianni et al., 1999, Bongianni et al., 2002, Guimond et al., 2003, Rovainen, 1977, Rovainen, 1983, Rovainen, 1985, Russell, 1986, Thompson, 1985 also for further references).
Recent studies in the in vitro brainstem preparation of the adult lamprey have shown that endogenously released excitatory amino acids are involved in the control of the timing and intensity components of the breathing pattern through an action on ionotropic and metabotropic glutamate receptors (Bongianni et al., 1999, Bongianni et al., 2002). More specifically, evidence has been provided as regards the fact that the respiratory activity in the lamprey is crucially dependent upon the activation of non-N-methyl-d-aspartate (non-NMDA) receptors, given that the blockade thereof completely suppresses the respiratory motor output (Bongianni et al., 1999).
On the other hand, the involvement of inhibitory amino acids in the respiratory control has recently been debated. In mammals, it has been proposed that the functional role of γ-aminobutyric acid (GABA) and glycine receptors becomes increasingly important during maturation (reviewed in Ballanyi et al., 1999, Ezure, 2004, Feldman et al., 2003, Haji et al., 2000, Richter and Spyer, 2001), although the results of some studies do not seem to entirely support this view (Büsselberg et al., 2001, Büsselberg et al., 2003, Johnson et al., 2002, Ramirez et al., 1996). To some extent, synaptic inhibition mediated by GABAA and glycine receptors has already been studied in the adult lamprey (Rovainen, 1983). However, only qualitative data have been provided, and assessments of changes in the timing and intensity components of the breathing-pattern induced by receptor blockades are lacking. Moreover, no information is available on the possible role played by GABAB and GABAC receptors in lamprey respiratory control.
This study was undertaken to quantitatively analyze the respiratory influences exerted by glycine receptors and by different subtypes of GABA receptors in the in vitro brainstem preparation of the adult lamprey. To this end, we investigated the respiratory responses to the bath application of specific antagonists. In addition, specific agonists were also employed to ascertain the effectiveness and selectivity of receptor blockade, as well as to provide further information on the respiratory role of inhibitory neurotransmission. The involvement of endogenously released GABA and glycine was also studied using specific uptake blockers.
Section snippets
Results
The amplitude of the integrated vagal nerve activity was taken as a reliable index of the intensity of respiratory bursts. With regard to the duration of respiratory bursts, these are characteristically very short in the lamprey when compared with those recorded in in vitro preparations from other lower vertebrates or mammals (see, e.g., Bou-Flores and Berger, 2001, Johnson et al., 2002, Lieske et al., 2000, Paton and Richter, 1995, Ramirez et al., 1996). In accordance with previous studies (
Discussion
This study provides a quantitative analysis of the respiratory responses caused by GABA and/or glycine receptor blockade in the adult lamprey. More specifically, the results increase current knowledge with regard to the role of GABAA and glycine receptors in the lamprey respiratory rhythmogenesis. Moreover, they provide data on the respiratory function of GABAB and GABAC receptors. The results support the notion that, at least in vitro, inhibitory synaptic mechanisms are not crucial for
Experimental procedure
All animal care and experimental procedures were conducted in accordance with the Italian legislation and the official regulations of the European Communities Council on the use of laboratory animals (directive 86/609/EEC). The study was approved by the Animal Care and Use Committee of the University of Florence.
Acknowledgments
We are grateful to Dr. Elisabeth Guerin for the English revision of the manuscript. This study was supported by grants from the Ministero dell'Istruzione, Università e Ricerca of Italy.
References (55)
- et al.
Respiratory network function in the isolated brainstem–spinal cord of newborn rats
Prog. Neurobiol.
(1999) - et al.
Role of glutamate receptor subtypes in the lamprey respiratory network
Brain Res.
(1999) - et al.
A combined blockade of glycine and calcium-dependent potassium channels abolishes the respiratory rhythm
Neuroscience
(2003) - et al.
Respiratory rhythm: an emergent network property?
Neuron
(2002) Reflections on respiratory rhythm generation
Prog. Brain Res.
(2004)- et al.
Anatomical and physiological study of respiratory motor innervation in lampreys
Neuroscience
(2003) - et al.
Neuropharmacology of control of respiratory rhythm and pattern in mature mammals
Pharmacol. Ther.
(2000) - et al.
The role of inhibitory amino acids in control of respiratory motor output in an arterially perfused rat
Respir. Physiol
(1992) - et al.
Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network
Neuropharmacology
(2004) - et al.
Pacemaker neurons and neuronal networks: an integrative view
Curr. Opin. Neurobiol.
(2004)
Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models
Trends Neurosci.
Generation of respiratory activity by the lamprey brain exposed to picrotoxin and strychnine, and weak synaptic inhibition in motoneurons
Neuroscience
GABAB receptor mediated effects on central respiratory system and their antagonism by phaclofen
Neurosci. Lett.
Glycine receptor-mediated fast synaptic inhibition in the brainstem respiratory system
Respir. Physiol.
Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model
Respir. Physiol.
Immunohistochemical distribution of tachykinins in the CNS of the lamprey Petromyzon marinus
J. Comp. Neurol.
Molecular structure and physiological functions of GABA(B) receptors
Physiol. Rev.
Group I and II metabotropic glutamate receptors modulate respiratory activity in the lamprey
Eur. J. Neurosci.
Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization
J. Neurophysiol.
Synaptic inhibition in the isolated respiratory network of neonatal rats
Eur. J. Neurosci.
Reorganisation of respiratory network activity after loss of glycinergic inhibition
Pflugers Arch.
Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation
J. Neurosci.
Possible roles of pacemaker neurons in mammalian respiratory rhythmogenesis
Cellular mechanisms underlying modulation of breathing pattern in mammals
Ann. N. Y. Acad. Sci.
Breathing: rhythmicity, plasticity, chemosensitivity
Annu. Rev. Neurosci.
Role of chloride-mediated inhibition in respiratory rhythmogenesis in an in vitro brainstem of tadpole, Rana catesbeiana
J. Physiol.
Comparative analysis of invertebrate central pattern generators
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