Coupled Oscillators Underlying Inspiration and Post‐Inspiration

Abstract

At rest, mammalians generate two phases of breathing: inspiration (I) and post‐inspiration (PI). These phases are thought to be generated by interacting inhibitory neurons in the Bӧtzinger complex (BӧtC) and preBӧtzinger complex (preBӧtC). Indeed transverse slices containing only the preBӧtC fail to generate PI and generate only I based on rhythmogenic neurons that express the transcription factor Dbx1. We employed a horizontal slice (HS) that keeps BӧtC and preBӧtC regions intact bilaterally, and two transverse slices at the levels of the BӧtC and preBӧtC, respectively. In the HS, the level of the BӧtC spontaneously generates PI population activity and is stimulated by norepinephrine. We show that the Dbx1 expression pattern extends throughout the preBӧtC and BӧtC areas forming a contiguous excitatory rhythmogenic column. Isolating the two areas retains respiratory rhythmic activity in both transverse slices. Photo‐stimulation of channelrhodopsin expressed in Dbx1 positive cells evokes network bursts in both preBӧtC and BӧtC transverse slices. Our data indicate that the two rhythms can function as independent oscillators and are coupled to generate I and PI in the HS. We conclude that the preBӧtC is not the only excitatory kernel, but instead forms an excitatory column containing the preBӧtC and BӧtC regions. Similar rhythm generating mechanisms determine rhythm generation along this column and phase relationships are established by GABAergic inhibition.