Eupnea and gasping differ in multiple aspects, including the mechanisms of neurogenesis. A ponto-medullary neuronal circuit is hypothesized to generate eupnea, whereas the gasp is generated by the discharge of medullary ÊpacemakerË neurones. These pacemaker mechanisms, which are likely to be suppressed during eupnea, are released in severe hypoxia to generate the gasp. We hypothesized that medullary neuronal activities, having discharge patterns consonant with generating the gasp, would continue periodic bursting following a blockade of synaptic transmission.
Activities of the phrenic nerve and single respiratory-modulated neurones, located in the ventrolateral medulla, were recorded extracellularly with glass microelectrodes (3M NaCl; 7-19 MV). Recordings were from the decerebrate, in situ preparation of the juvenile rat (see Paton 1996, for full details and initial anaesthesia). During eupnea, the preparation was perfused with a solution equilibrated with a hyperoxic-normocapnic gas mixture (95 % oxygen and 5 % carbon dioxide). Gasping was produced by switching to a separate perfusate equilibrated with a hypoxic (5 % oxygen) hypercapnic (8 % carbon dioxide) gas mixture.
In eupnea, neurones had ÊinspiratoryË, ÊexpiratoryË or Êphase-spanningË patterns. In gasping, many neuronal activities either discharged during the phrenic burst or ceased firing. However, others that were inspiratory or expiratory-inspiratory phase-spanning in eupnea, became Êpre-inspiratoryË in gasping, with discharge commencing before the phrenic burst. These Êpre-inspiratoryË neurones were recorded following a blockade of synaptic transmission. This blockade was produced by adding antagonists to the perfusate to block both inhibitory (glycine and GABAA receptors: strychnine, 1 µM; bicuculline-free-base, 20 µM respectively) and excitatory (NMDA and non-NMDA receptors: (RS)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid or CPP, 10 µM; kynurenic acid, 2.5-6.0 mM) neurotransmission. Kynurenic acid was added in increments until phrenic activity ceased. These concentrations were based upon other studies in which synaptic events were abolished in intracellularly recorded respiratory-modulated hypoglossal neurones. In 13 neurones tested, 8 exhibited periodic bursting during hypoxia. Of these 8, four neurones also displayed bursting in hyperoxia. The five other neurones remained silent.
We conclude that neuronal activities, compatible with generating gasping, can discharge by intrinsic pacemaker mechanisms. These neuronal activities may underlie the neurogenesis of the gasp.
British Heart Foundation and NIH funded research