Effects of Voluntary Locomotion and Calcitonin Gene-Related Peptide on the Dynamics of Single Dural Vessels in Awake Mice.

The dura mater is a vascularized membrane surrounding the brain and is heavily innervated by sensory nerves. Our knowledge of the dural vasculature has been limited to pathological conditions, such as headaches, but little is known about the dural blood flow regulation during behavior. To better understand the dynamics of dural vessels during behavior, we used two-photon laser scanning microscopy (2PLSM) to measure the diameter changes of single dural and pial vessels in the awake mouse during voluntary locomotion. Surprisingly, we found that voluntary locomotion drove the constriction of dural vessels, and the dynamics of these constrictions could be captured with a linear convolution model. Dural vessel constrictions did not mirror the large increases in intracranial pressure (ICP) during locomotion, indicating that dural vessel constriction was not caused passively by compression. To study how behaviorally driven dynamics of dural vessels might be altered in pathological states, we injected the vasodilator calcitonin gene-related peptide (CGRP), which induces headache in humans. CGRP dilated dural, but not pial, vessels and significantly reduced spontaneous locomotion but did not block locomotion-induced constrictions in dural vessels. Sumatriptan, a drug commonly used to treat headaches, blocked the vascular and behavioral the effects of CGRP. These findings suggest that, in the awake animal, the diameters of dural vessels are regulated dynamically during behavior and during drug-induced pathological states. SIGNIFICANT STATEMENT The vasculature of the dura has been implicated in the pathophysiology of headaches, but how individual dural vessels respond during behavior, both under normal conditions and after treatment with the headache-inducing peptide calcitonin gene-related peptide (CGRP), is poorly understood. To address these issues, we imaged individual dural vessels in awake mice and found that dural vessels constricted during voluntary locomotion, and this constriction did not follow locomotion-induced intracranial pressure increases. CGRP injection caused baseline dural vessel dilation and reduced locomotion but did not block locomotion-induced constrictions of dural vessels or affect pial vessels. These novel findings reveal dynamic regulation of dural vessels that are distinct from those in cerebral blood vessels during both normal behavior and after dilation by CGRP.