M. S. Sandhu, D. M. Baekey, N. G. Maling, J. C. Sanchez, P. J. Reier, D. D. Fuller

Anatomical evidence indicates that mid-cervical interneurons can be synaptically coupled with phrenic motoneurons. Accordingly, we hypothesized that interneurons in the C3-4 spinal cord can display discharge patterns temporally linked with inspiratory phrenic motor output. Anesthetized adult rats were studied before, during and after a 4-min bout of moderate hypoxia. Neuronal discharge in C3-4 lamina I-IX was monitored using a multi-electrode array while phrenic nerve activity was extracellularly recorded. For the majority of cells, spike triggered averaging (STA) of ipsilateral inspiratory phrenic nerve activity based on neuronal discharge provided no evidence of discharge synchrony. However, a distinct STA phrenic peak with a 6.83±1.1 ms lag was present for 5% of neurons, a result which indicates a monosynaptic connection with phrenic motoneurons. The majority (93%) of neurons changed discharge rate during hypoxia, and the diverse responses included both increased and decreased firing. Hypoxia did not change the incidence of STA peaks in the phrenic nerve signal. Following hypoxia, 40% of neurons continued to discharge at rates above pre-hypoxia values (i.e., short-term potentiation, STP), and cells with initially low discharge rates were more likely to show STP (P<0.001). We conclude that a population of non-phrenic C3-4 neurons in the rat spinal cord is synaptically coupled to the phrenic motoneuron pool, and these cells can modulate inspiratory phrenic output. In addition, the C3-4 propriospinal network shows a robust and complex pattern of activation both during and following an acute bout of hypoxia.