Sigh and Eupnea Rhythmogenesis Involve Distinct Interconnected Subpopulations: A Combined Computational and Experimental Study

Natalia Toporikova, Marc Chevalier, Muriel Thoby-Brisson
eneuro. 2015-03-01; 2(2): ENEURO.0074-14.2015
DOI: 10.1523/eneuro.0074-14.2015

Lire sur PubMed

1. eNeuro. 2015 Apr 22;2(2). pii: ENEURO.0074-14.2015. doi:
10.1523/ENEURO.0074-14.2015. eCollection 2015 Mar-Apr.

Sigh and Eupnea Rhythmogenesis Involve Distinct Interconnected Subpopulations: A
Combined Computational and Experimental Study

Toporikova N(1), Chevalier M(2), Thoby-Brisson M(2).

Author information:
(1)Department of Biology, Washington and Lee University , Lexington, Virginia
(2)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR
5287 , Université de Bordeaux , 33076 Bordeaux, France.

Neural networks control complex motor outputs by generating several rhythmic
neuronal activities, often with different time scales. One example of such a
network is the pre-Bötzinger complex respiratory network (preBötC) that can
simultaneously generate fast, small-amplitude, monophasic eupneic breaths
together with slow, high-amplitude, biphasic augmented breaths (sighs). However,
the underlying rhythmogenic mechanisms for this bimodal discharge pattern remain
unclear, leaving two possible explanations: the existence of either reconfiguring
processes within the same network or two distinct subnetworks. Based on recent in
vitro data obtained in the mouse embryo, we have built a computational model
consisting of two compartments, interconnected through appropriate synapses. One
compartment generates sighs and the other produces eupneic bursts. The model
reproduces basic features of simultaneous sigh and eupnea generation (two types
of bursts differing in terms of shape, amplitude, and frequency of occurrence)
and mimics the effect of blocking glycinergic synapses. Furthermore, we used this
model to make predictions that were subsequently tested on the isolated preBötC
in mouse brainstem slice preparations. Through a combination of in vitro and in
silico approaches we find that (1) sigh events are less sensitive to network
excitability than eupneic activity, (2) calcium-dependent mechanisms and the Ih
current play a prominent role in sigh generation, and (3) specific parameters of
Ih activation set the low sensitivity to excitability in the sigh neuronal
subset. Altogether, our results strongly support the hypothesis that distinct
subpopulations within the preBötC network are responsible for sigh and eupnea

DOI: 10.1523/ENEURO.0074-14.2015
PMCID: PMC4596094
PMID: 26464980

Auteurs Bordeaux Neurocampus