FIGURE 4.

Rhythmogenic roles of excitatory and inhibitory neurons in the mammalian breathing CPG

A: the pre-Bötzinger Complex (preBötC) continues to produce a rhythm (purple) that is in phase with inspiratory hypoglossal (XII) motor output (black) when isolated in medullary slices from neonatal mice. The preBötC is also active in phase with inspiratory motor activity in intact adult mice. B: excitatory (red) and inhibitory (blue) preBötC neurons are concurrently active in phase with rhythmic inspiratory activity (purple). Intracellular current-clamp recordings of genetically identified Dbx1+ (excitatory) and Vgat+ (inhibitory) neurons active with integrated extracellular preBötC population bursts generated in vitro. C: optogenetic stimulation of excitatory (Dbx1+) or inhibitory (Vgat+) preBötC neurons resets the breathing rhythm in vivo and in vitro. Stimulations can advance or delay the next inspiratory cycle depending on stimulus phase (I, inspiratory phase; E, expiratory phase). Note that postinhibitory rebound advances the next cycle during relatively slow rhythms in vitro but not in vivo. Figure adapted from Ref. 9, with permission from Nature Communications.