Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized rats

Abstract

Retrotrapezoid (RTN) neurons sustain breathing automaticity. These neurons have chemoreceptor properties but their firing is also regulated by multiple synaptic inputs of uncertain function. Here we test whether RTN, like neighboring presympathetic neurons, are excited by somatic afferent stimulation. Experiments were performed in Inactin-anesthetized, bilaterally-vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats. End-expiratory CO2 (eeCO2) was varied between 4 and 10% to modify rate and amplitude of phrenic nerve discharge (PND). RTN and presympathetic neurons were recorded extracellularly below the facial motor nucleus using established criteria. Sciatic nerve stimulation (SNstim, 1 ms, 0.5Hz) slightly increased blood pressure (6.6 ± 1.6 mmHg) and heart rate and, at low eeCO2 (<5.5%), entrained PND. Ipsi- and contralateral SNstim produced the known biphasic activation of presympathetic neurons. SNstim evoked a similar but weaker biphasic response in up to 67% of RTN neurons and monophasic excitation in the rest. At low eeCO2, RTN neurons were silent and responded more weakly to SNstim than at high eeCO2. RTN neuron firing was respiratory modulated to various degrees. The phasic activation of RTN neurons elicited by SNstim was virtually unchanged at high eeCO2 when PND entrainment to the stimulus was disrupted. Thus, RTN neuron response to SNstim did not result from entrainment to the central pattern generator. Overall, SNstim shifted the relationship between RTN firing and eeCO2 upward. In conclusion, somatic afferent stimulation increases RTN neuron firing probability without altering their response to CO2. This pathway may contribute to the hyperpnea triggered by nociception, exercise (muscle metabotropic reflex) or hyperthermia.