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

In an excised Wistar rat medulla-spinal cord block preparation we previously found that dopamine slows respiratory rhythm by activation of dopamine D-4 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 D-4 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 D-4 receptors. We found that approximately 60% of Pre-I neurons express dopamine D-4 receptors. These results show that dopaminergic respiratory rhythm depression is due to dispersion of synchronized Pre-I driving of I neurons caused by dopamine D-4 receptor stimulation of Pre-I neurons.