Hypoxia-induced respiratory patterned activity in Lymnaea originates at the periphery

Respiration in Lymnaea is a hypoxia-driven rhythmic behavior, which is cont rolled by an identified network of central pattern generating (CPG) neurons . However, the precise site(s) (i.e., central or peripheral) at which hypox ia acts and the cellular mechanisms by which the respiratory chemosensory d rive is conveyed to the CPG were previously unknown. Using semi-intact and isolated ganglionic preparations, we provide the first direct evidence that the hypoxia-induced respiratory drive originates at the periphery (not wit hin the central ring ganglia) and that it is conveyed to the CPG neurons vi a the right pedal dorsal neuron 1 (RPeD1). The respiratory discharge freque ncy increased when the periphery, but not the CNS, was made hypoxic. We fou nd that in the semi-intact preparations, the frequency of spontaneously occ urring respiratory bursts was significantly lower than in isolated ganglion ic preparations. Thus the periphery exerts a suppressive regulatory control on respiratory discharges in the intact animal. Moreover, both anoxia (0% O-2) and hypercapnia (10% CO2) produce a reduction in respiratory discharge s in semi-intact, but not isolated preparations. However, the effects of CO 2 may be mediated through pH changes of the perfusate. Finally, we demonstr ate that chronic exposure of the animals to hypoxia (90% N-2), prior to int racellular recordings, significantly enhanced the rate of spontaneously occ urring respiratory discharges in semi-intact preparations, even if they wer e maintained in normoxic saline for several hours. Moreover, we demonstrate that the peripherally originated hypoxia signal is likely conveyed to the CPG neurons via RPeD1. In summary, the data presented in this study demonst rate the important role played by the periphery and the RPeD1 neuron in reg ulating respiration in response to hypoxia in Lymnaea.