Emergence of sigh rhythmogenesis in the embryonic mouse
J Physiol. 2014-03-21; 592(10): 2169-2181
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1. J Physiol. 2014 May 15;592(10):2169-81. doi: 10.1113/jphysiol.2013.268730. Epub
2014 Mar 3.
Emergence of sigh rhythmogenesis in the embryonic mouse.
Chapuis C(1), Autran S(2), Fortin G(2), Simmers J(1), Thoby-Brisson M(3).
(1)University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives
d’Aquitaine, CNRS UMR 5287, 33076 Bordeaux, France.
(2)Institut de Neurobiologie Alfred Fessard, Neurobiology and Development, CNRS
UPR 3294, 91190 Gif sur Yvette, France.
(3)University of Bordeaux, Institut de Neurosciences Cognitives et Intégratives
d’Aquitaine, CNRS UMR 5287, 33076 Bordeaux, France
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.
© 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
PMID: 24591570 [Indexed for MEDLINE]