Sigh generation in preBötzinger Complex

We explored neural mechanisms underlying sighing. Photostimulation of parafacial (pF) neuromedin B (NMB) or gastrin releasing peptide (GRP), or preBotzinger Complex (preBotC) NMBR or GRPR neurons elicited ectopic sighs with latency inversely related to time from preceding endogenous sigh. Of particular note, ectopic sighs could be produced without involvement of these peptides or their receptors in preBotC. Moreover, chemogenetic or optogenetic activation of preBotC SST neurons induced sighing, even in the presence of NMBR and/or GRPR antagonists. We propose that an increase in the excitability of preBotC NMBR or GRPR neurons not requiring activation of their peptide receptors activates partially overlapping pathways to generate sighs, and that preBotC SST neurons are a downstream element in the sigh generation circuit that converts normal breaths into sighs.