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This Article Full Text Full Text (PDF) All Versions of this Article: 551/3/981    most recent jphysiol.2003.048157v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, Y. Articles by Ling, L. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Ling, L.

Episodic phrenic-inhibitory vagus nerve stimulation paradoxically induces phrenic long-term facilitation in rats

Yi Zhang, Michelle McGuire, David P. White and Liming Ling

All respiratory long-term facilitation (LTF) is induced by inspiratory-excitatory stimulation, suggesting that LTF needs inspiratory augmentation and is the result of a Hebbian mechanism (coincident pre- and post-synaptic activity strengthens synapses). The present study examined the long-term effects of episodic inspiratory-inhibitory vagus nerve stimulation (VNS) on phrenic nerve activity. We hypothesized that episodic VNS would induce phrenic long-term depression. The results are compared with those obtained following serotonin receptor antagonism or episodic carotid sinus nerve stimulation (CSNS). Integrated phrenic neurograms were measured before, during and after three episodes of 5 min VNS (50 Hz, 0.1 ms), each separated by a 5 min interval, at a low (~50 µA), medium (~200 µA) or high (~500 µA) stimulus intensity in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats. Medium- and high-intensity VNS eliminated rhythmic phrenic activity during VNS, while low-intensity VNS only reduced phrenic burst frequency. At 60 min post-VNS, phrenic amplitude was higher than baseline (35 ± 5 % above baseline, mean ± S.E.M., P < 0.05) in the high-intensity group but not in the low- (-4 ± 4 %) or medium-intensity groups (-10 ± 15 %), or in the high-intensity with methysergide group (4 mg kg^-1, I.P.) (-11 ± 5 %). These data, which are inconsistent with our hypothesis, indicate that phrenic-inhibitory VNS induces a serotonin-dependent phrenic LTF similar to that induced by phrenic-excitatory CSNS (33 ± 7 %) and may require activation of high-threshold afferent fibres. These data also suggest that the synapses on phrenic motoneurons do not use the Hebbian mechanism in this LTF, as these motoneurons were suppressed during VNS.

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