Dopaminergic regulation of cerebral cortical microcirculation

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Abstract

Functional variations in cerebral cortical activity are accompanied by local changes in blood flow, but the mechanisms underlying this physiological coupling are not well understood. Here we report that dopamine, a neurotransmitter normally associated with neuromodulatory actions, may directly affect local cortical blood flow. Using light and electron-microscopic immunocytochemistry, we show that dopaminergic axons innervate the intraparenchymal microvessels. We also provide evidence in an in vitro slice preparation that dopamine produces vasomotor responses in the cortical vasculature. These anatomical and physiological observations reveal a previously unknown source of regulation of the microvasculature by dopamine. The findings may be relevant to the mechanisms underlying changes in blood flow observed in circulatory and neuropsychiatric disorders.

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Figure 1: Distribution of close appositions of dopamine-transporter-labeled axons on all blood vessels in a section through cortical layers I-IIIa in area 9.
Figure 2: High-power photographs of dopaminergic terminals associated with small cortical blood vessels.
Figure 3: Correlated light- and electron-microscopic analysis of dopamine terminals associated with the microvasculature.
Figure 4: Catecholaminergic innervation of pial arteries.
Figure 5: DIC videomicroscopic images of cortical microvessels responding to perivascular iontophoretic application of dopamine with +10 to +60 nA current in ferret prefrontal cortical slices.

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Acknowledgements

We thank Klara Szigeti for preparing tissue for electron microscopy, and David McCormick for providing us with ferret frontal cortex for the physiological experiments. This work was supported by MH44866 and a Pfizer Postdoctoral Fellowship to ECM.

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Correspondence to Patricia S. Goldman-Rakic.

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