Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the PreBotzinger complex

Neurokinin-1 receptor (NK1R) and mu-opioid receptor (mu OR) agonists affected respiratory rhythm when injected directly into the preBotzinger Complex (preBotC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBotC rhythmogenic neurons. The distribution of NK1R(+) neurons anatomically defined the preBotC. Type 1 neurons in the preBotC, which have rhythmogenic properties, expressed both NK1Rs and mu ORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBotC is a definable anatomic structure with unique physiological function and that a subpopulation of neurons expressing both NK1Rs and mu ORs generate respiratory rhythm and modulate respiratory frequency.