title: Emergence of sigh rhythmogenesis in the embryonic mouse.
abstract: In mammals, eupnoeic breathing is periodically interrupted by spontaneous augmented breaths (sighs) that include a larger-amplitude inspiratory effort, typically followed by a post-sigh apnoea. Previous in vitro studies in newborn rodents have demonstrated that the respiratory oscillator of the pre-Bötzinger complex (preBötC) can generate the distinct inspiratory motor patterns for both eupnoea- and sigh-related behaviour. During mouse embryonic development, the preBötC begins to generate eupnoeic rhythmicity at embryonic day (E) 15.5, but the network's ability to also generate sigh-like activity remains unexplored at prenatal stages. Using transverse brainstem slice preparations we monitored the neuronal population activity of the preBötC at different embryonic ages. Spontaneous sigh-like rhythmicity was found to emerge progressively, being expressed in 0/32 slices at E15.5, 7/30 at E16.5, 9/22 at E17.5 and 23/26 at E18.5. Calcium imaging showed that the preBötC cell population that participates in eupnoeic-like discharge was also active during fictive sighs. However, patch-clamp recordings revealed the existence of an additional small subset of neurons that fired exclusively during sigh activity. Changes in glycinergic inhibitory synaptic signalling, either by pharmacological blockade, functional perturbation or natural maturation of the chloride co-transporters KCC2 or NKCC1 selectively, and in an age-dependent manner, altered the bi-phasic nature of sigh bursts and their coordination with eupnoeic bursting, leading to the generation of an atypical monophasic sigh-related event. Together our results demonstrate that the developmental emergence of a sigh-generating capability occurs after the onset of eupnoeic rhythmogenesis and requires the proper maturation of chloride-mediated glycinergic synaptic transmission.
authors.affiliation: University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, 33076 Bordeaux, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Chapuis
authors.affiliation: Institut de Neurobiologie Alfred Fessard, Neurobiology and Development, CNRS UPR 3294, 91190 Gif sur Yvette, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Autran
authors.affiliation: Institut de Neurobiologie Alfred Fessard, Neurobiology and Development, CNRS UPR 3294, 91190 Gif sur Yvette, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Fortin
authors.affiliation: University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, 33076 Bordeaux, France.
authors.forename: John
authors.initials: J
authors.lastname: Simmers
authors.affiliation: University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR 5287, 33076 Bordeaux, France muriel.thoby-brisson@u-bordeaux.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Thoby-Brisson
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D001933:Brain Stem / Q000196:embryology* / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D012135:Respiratory Sounds / Q000502:physiology*