Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity

All medullary central chemoreceptor sites contain neurokinin-1 receptor immunoreactivity (NK1R-ir). We ask if NK1R-ir neurons and processes are involved in chemoreception. At one site, the retrotrapezoid nucleus/parapyramidal region (RTN/Ppy), we injected a substance P-saporin conjugate (SP-SAP; 0.1 pmol in 100 nl) to kill NK1R-ir neurons specifically, or SAP alone as a control. We made measurements for 15 days after the injections in two groups of rats. In group 1, with unilateral injections made in the awake state via a pre-implanted guide cannula, we compared responses within rats using initial baseline data. In group 2, with bilateral injections made under anaesthesia at surgery, we compared responses between SP-SAP- and SAP-treated rats. SP-SAP treatment reduced the volume of the RTN/Ppy region that contained NK1R-ir neuronal somata and processes by 44% (group 1) and by 47 and 40% on each side, respectively (group 2). Ventilation ((V)over dot(E)) and tidal volume (V-T) were decreased during air breathing in sleep and wakefulness (group 2; P<0.001; two-way ANOVA) and P-a,P-CO2 was increased (group 2; P<0.05; Student's t test). When rats breathed an air mixture containing 7% CO2 during sleep and wakefulness, (V)over dot(E) and V-T were lower (groups 1 and 2; P<0.001; ANOVA) and the Δ(V)over dot(E) in air containing 7% CO2 compared to air was decreased by 28-30% (group 1) and 17-22% (group 2). SP-SAP-treated rats also slept less during air breathing. We conclude that neurons with NK1R-ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal.