Dopamine: The Link Between Neuronal Activity And Blood Flow

That brain activity increases cerebral blood flow has been known for a long time. Angelo Mosso, an Italian physiologist, documented this observation in the late 1800s. In his La Temperatura del Cervello, Mosso writes: "Mr Cane was resting peacefully when... I said just a few words expressing the impression that his wife had made upon me when I first saw her. Cane did not speak. The blood to the brain increased immediately and the volume of the feet markedly diminished." What Mosso had observed and recorded actually reflects how an emotional stimulus had caused cerebral vasodilatation and peripheral vasoconstriction.

As physiological mechanisms in the body tend to be, such a link between brain activity and cerebral blood flow is logical. Brain activity entails neuronal activation, that is neurons getting all fired up and transmitting a series of electric impulses along their axons. The electric impulses are basically different flows of ions orchestrated by cellular ion pumps. And for ion pumps to properly act as conductors, energy is required. Where does this energy come from? Why, blood of course. In effect, this means that when neurons start firing, they require an increased supply of energy which is obtained by increasing the supply of blood. To put this in perspective, when a particular part of the brain is functionally activated, cerebral blood flow to that particular part is increased to cater for the increased metabolic requirement.

So what exactly is it that ties neuronal activity to the cerebral blood flow? What exactly is happening in the brain which enables this activity-dependent regulation of blood flow? It has been proposed that neurons release vasoactive agents in extracellular spaces. These agents then diffuse to reach blood vessels ultimately changing their diameters by vasoconstriction or vasodilatation. While this does actually happen, it cannot account for the rapidity and spatial definition of increases in cerebral blood flow produced by neuronal activity. Therefore, another more direct (primary) mechanism seems to be in place.

It was not until 1998 that this primary mechanism would be uncovered. In a paper published in Nature Neuroscience, Krimmer et al. (1998) found that axons immunopositive for dopamine or dopamine transporter were in close apposition to blood vessels in the frontal lobe of rhesus monkeys. To be more specific, they found that the dopaminergic fibers were in contact with both penetrating arterioles and capillaries. But they didn't stop there. Krimmer and colleagues tested the response of some cerebral arteries to perivascular microapplication of dopamine in vitro and recorded dose-dependent vasoconstriction in more than half of their specimen. Therefore, Krimmer and colleagues had shown that not only was dopamine a neurotransmitter used by a number of neurons in the frontal cortex but also that it worked as a vasopressor.

From this study, it would appear that dopamine has a direct effect on cerebral blood vessels and thus in the control of local cerebral cortical blood flow. Why is the study important? The concluding paragraph of Iadecola's (1998) commentary on the study summaries its importance perfectly so I'll paste part of it below:

The close association between dopaminergic terminals and cerebral blood vessels raises the possibility that disturbances in central dopaminergic neurotransmission could alter cerebrovascular regulation [...]. For example, cerebral blood flow and its regulation are abnormal in schizophrenia, depression and Parkinsonism, diseases in which there is dysfunction of dopaminergic pathways. In particular, in schizophrenia, alterations in blood flow in the frontal lobe often parallel the clinical manifestations of the disease. Considering the rich perivascular dopaminergic terminals in the frontal cortex, it is likely that alterations in the dopaminergic vascular innervation contribute to the vascular disturbances observed in these conditions.

Dopamine never ceases to amaze me.

Image credit: djneight (from flickr)

References:

Iadecola, C. Neurogenic control of the cerebral microcirculation: is dopamine minding the store? Nature Neuroscience 1, 263-265 (1998).

Iadecola, C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nature Reviews Neuroscience 5, 347-360 (2004).

Krimer, L. S.et al. Dopaminergic regulation of cerebral cortical microcirculation. Nature Neuroscience 1, 286-289 (1998).