title: Neuronal mechanisms of respiratory pattern generation are evolutionary conserved.
abstract: A brainstem region, the paratrigeminal respiratory group (pTRG), has been suggested to play a crucial role in the respiratory rhythm generation in lampreys. However, a detailed characterization of the pTRG region is lacking. The present study performed on isolated brainstem preparations of adult lampreys provides a more precise localization of the pTRG region with regard to both connectivity and neurochemical markers. pTRG neurons projecting to the vagal motoneuronal pool were identified in a restricted area of the rostral rhombencephalon at the level of the isthmic Müller cell I1 close to sulcus limitans of His. Unilateral microinjections of lidocaine, muscimol, or glutamate antagonists into the pTRG inhibited completely the bilateral respiratory activity. In contrast, microinjections of glutamate agonists enhanced the respiratory activity, suggesting that this region is critical for the respiratory pattern generation. The retrogradely labeled pTRG neurons are glutamatergic and surrounded by terminals with intense substance P immunoreactivity. Cholinergic neurons were seen close to, and intermingled with, pTRG neurons. In addition, α-bungarotoxin binding sites (indicating nicotinic receptors) were found throughout the pTRG area and particularly on the soma of these neurons. During apnea, induced by blockade of ionotropic glutamate receptors within the same region, microinjections of 1 μm substance P or 1 mm nicotine into the pTRG restored rhythmic respiratory activity. The results emphasize the close similarities between the pTRG and the mammalian pre-Bötzinger complex as a crucial site for respiratory rhythmogenesis. We conclude that some basic features of the excitatory neurons proposed to generate respiratory rhythms are conserved throughout evolution.
authors.affiliation: Department of Physiological Sciences, University of Florence, I-50134 Florence, Italy.
authors.forename: Elenia
authors.initials: E
authors.lastname: Cinelli
authors.forename: Brita
authors.initials: B
authors.lastname: Robertson
authors.forename: Donatella
authors.initials: D
authors.lastname: Mutolo
authors.forename: Sten
authors.initials: S
authors.lastname: Grillner
authors.forename: Tito
authors.initials: T
authors.lastname: Pantaleo
authors.forename: Fulvia
authors.initials: F
authors.lastname: Bongianni
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D066298:In Vitro Techniques; D007798:Lampreys; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012125:Respiratory Center / Q000166:cytology* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D018683:Excitatory Amino Acid Agents; C070614:neurobiotin; D013373:Substance P; D001710:Biotin; D002795:Choline O-Acetyltransferase