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The Journal of Neuroscience, April 27, 2005, 25(17):4307-4318; doi:10.1523/JNEUROSCI.0551-05.2005

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Behavioral/Systems/Cognitive
Emergence of the Pre-Bötzinger Respiratory Rhythm Generator in the Mouse Embryo

Muriel Thoby-Brisson, Jean-Baptiste Trinh, Jean Champagnat, and Gilles Fortin

Laboratoire de Neurobiologie Génétique et Intégrative, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif sur Yvette, France

To obtain insights into the emergence of rhythmogenic circuits supporting respiration, we monitored spontaneous activities in isolated brainstem and medullary transverse slice preparations of mouse embryos, combining electrophysiological and calcium imaging techniques. At embryonic day 15 (E15), in a restricted region ventral to the nucleus ambiguus, we observed the onset of a sustained high-frequency (HF) respiratory-like activity in addition to a preexisting low-frequency activity having a distinct initiation site, spatial extension, and susceptibility to gap junction blockers. At the time of its onset, the HF generator starts to express the neurokinin 1 receptor, is connected bilaterally, requires active AMPA/kainate glutamatergic synapses, and is modulated by substance P and the µ-opioid agonist D-Ala²-N-Me-Phe⁴-Glycol⁵-enkephalin. We conclude that a rhythm generator sharing the properties of the neonatal pre-Bötzinger complex becomes active during E15 in mice.

Key words: mouse hindbrain; embryo; rhythm; respiration; calcium imaging; pre-Bötzinger complex

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Received Feb 10, 2005; revised March 15, 2005; accepted March 21, 2005.

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