Intrinsic and synaptic mechanisms controlling the expiratory activity of excitatory lateral parafacial neurones of rats

Active expiration is essential for increasing pulmonary ventilation during high chemical drive (hypercapnia). The lateral parafacial (pF(L)) region, which contains expiratory neurones, drives abdominal muscles during active expiration in response to hypercapnia. However, the electrophysiological properties and synaptic mechanisms determining the activity of pF(L) expiratory neurones, as well as the specific conditions for their emergence, are not fully understood. Using whole cell electrophysiology and single cell quantitative RT-PCR techniques, we describe the intrinsic electrophysiological properties, the phenotype and the respiratory-related synaptic inputs to the pF(L) expiratory neurones, as well as the mechanisms for the expression of their expiratory activity under conditions of hypercapnia-induced active expiration, using in situ preparations of juvenile rats. We also evaluated whether these neurones possess intrinsic CO2/[H+] sensitivity and burst generating properties. GABAergic and glycinergic inhibition during inspiration and expiration suppressed the activity of glutamatergic pF(L) expiratory neurones in normocapnia. In hypercapnia, these neurones escape glycinergic inhibition and generate burst discharges at the end of expiration. Evidence for the contribution of post-inhibitory rebound, Ca(V)3.2 isoform of T-type Ca2+ channels and intracellular [Ca2+] is presented. Neither intrinsic bursting properties, mediated by persistent Na+ current, nor CO2/[H+] sensitivity or expression of CO2/[H+] sensitive ion channels/receptors (TASK or GPR4) were observed. On the other hand, hyperpolarisation-activated cyclic nucleotide-gated and twik-related K+ leak channels were recorded. Post-synaptic disinhibition and the intrinsic electrophysiological properties of glutamatergic neurones play important roles in the generation of the expiratory oscillations in the pF(L) region during hypercapnia in rats. Key points Hypercapnia induces active expiration in rats and the recruitment of a specific population of expiratory neurones in the lateral parafacial (pF(L)) region. Post-synaptic GABAergic and glycinergic inhibition both suppress the activity of glutamatergic pF(L) neurones during inspiratory and expiratory phases in normocapnia. Hypercapnia reduces glycinergic inhibition during expiration leading to burst generation by pF(L) neurones; evidence for a contribution of post-inhibitory rebound, voltage-gated Ca2+ channels and intracellular [Ca2+] is presented. pF(L) glutamatergic expiratory neurones are neither intrinsic burster neurones, nor CO2/[H+] sensors, and do not express CO2/[H+] sensitive ion channels or receptors. Post-synaptic disinhibition and the intrinsic electrophysiological properties of glutamatergic neurones both play important roles in the generation of the expiratory oscillations in the pF(L) region during hypercapnia in rats.

Automated summary

In this study, we investigated the electrophysiological properties and synaptic mechanisms of pF(L) expiratory neurones in juvenile rats. GABAergic and glycinergic inhibition in normocapnia suppressed the activity of glutamatergic pF(L) expiratory neurones, while in hypercapnia, these neurones generated burst discharges at the end of expiration by escaping glycinergic inhibition. Post-synaptic disinhibition and intrinsic electrophysiological properties of glutamatergic neurones played important roles in generating expiratory oscillations in the pF(L) region during hypercapnia in rats.