Dopamine desynchronizes the pace‐making neuronal activity of rat respiratory rhythm generation

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Abstract
In an excised Wistar rat medulla‐spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D4 receptors [Fujii et al., (2004)Neurosci. Res., 50, 355–359.] In the present paper, we investigated the effect of dopamine on pre‐inspiratory (Pre‐I) and inspiratory (I) neurons using the combination of an optical recording technique with a voltage‐sensitive dye, unit recording and patch‐clamp recording. Optical imaging of the ventral surface of the block preparation disclosed different locations and activity patterns of Pre‐I and I neurons. In addition to slowing the rhythm, dopamine depressed respiratory activity of Pre‐I neurons collectively but not that of I neurons. The dopaminergic suppression of Pre‐I neurons was mimicked by a dopamine D4 receptor agonist, PD168077. Unit recording and patch‐clamp recording demonstrated that dopamine depolarizes Pre‐I neurons, disperses Pre‐I firing and depresses Pre‐I phase postsynaptic potentials (PSPs) of I neurons. Immunohistological investigation revealed that Pre‐I neurons express dopamine D4 receptors. We found that approximately 60% of Pre‐I neurons express dopamine D4 receptors. These results show that dopaminergic respiratory rhythm depression is due to dispersion of synchronized Pre‐I driving of I neurons caused by dopamine D4 receptor stimulation of Pre‐I neurons.