Figure 1. Perinatal mouse hindbrain produces temporally coordinated respiratory output from cervical and lumbar motor pools, as well as internal intercostal respiratory muscles.
(A) Cartoon of sagittal view through caudal hindbrain indicating the locations of distinct developmentally defined glutamatergic populations important for breathing. Colored filled circles indicate the relative location of rhombic lip (RL) Atoh1 (orange), RTN Phox2b (purple), and Dbx1 (blue) derived neurons. Note: RTN Phox2b neurons transiently express Atoh1, but we have left this out for clarity. Atoh1 RL neurons do not express Phox2b and have not been shown to be chemosensitive. The green circle identifies the location of preBötzinger Complex (preBötC) Dbx1 neurons hypothesized to generate the cervical (inspiratory) rhythm. The magenta rectangle indicates the location of Retrotrapezoid/Parafacial respiratory group (RTN/pFRG) region neurons hypothesized to generate independent lumbar (expiratory) rhythm. LRN–lateral reticular nucleus, NA–nucleus ambiguus, rVRG–rostral ventral respiratory group, VIIn (VII motor nucleus). Scale bar = 200 µm. (B) Schematic describing the hypothesized glutamatergic coupling between Dbx1 preBötC neurons generating inspiration (green circle–right) and the three candidate glutamatergic RTN/pFRG populations generating expiration (magenta rectangle–left). Colored circles indicate genetic lineage as in (A). (C) Electrophysiological traces (upper–integrated, lower–raw) of spontaneous respiratory-related output from cervical (C4, green) and lumbar (L1, magenta) motor roots as well as EMG recording from the XIth internal intercostal muscle (IC). Cervical roots innervate the diaphragm active during inspiration. Lumbar roots innervate abdominal respiratory muscles active during expiration in adults. Arrows indicate respiratory-related bursts where some respiratory motor pools lack activity. (D) In some fictive breaths, cervical (green), lumbar (magenta), and IC (black) motor outputs are active nearly simultaneously. (E) In other fictive breaths only the cervical root is active. (F–I) Single integrated C-L-IC fictive breaths showing breath-by-breath variations in temporal co-activation between respiratory motor outputs. Note that in some respiratory bursts (G–I) both lumbar (magenta) and IC (black) burst peaks occur before the cervical burst. Also IC activity can occur during both cervical and lumbar bursts (H–I). (J–K) Cartoons indicating how different patterns of respiratory motor output from cervical and lumbar motor pools could be produced by changes in the synaptic strengths of excitatory (dots) or inhibitory (arrowheads) synaptic connections between the putative preBötC Dbx1 inspiratory oscillator, the unknown RTN/pFRG expiratory oscillator, and intervening inhibitory interneurons. Solid lines indicate strong connections, dotted lines indicate weaker connection. Scale bar = 10 s (C), 500 ms (D–I).