Spatial and temporal dynamics of cerebral blood vessels during voluntary locomotion in health and disease
Open Access
- Author:
- Gao, Yurong
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 02, 2015
- Committee Members:
- Patrick James Drew, Dissertation Advisor/Co-Advisor
Patrick James Drew, Committee Chair/Co-Chair
Kevin Douglas Alloway, Committee Member
Timothy J Jegla, Committee Member
Yu Zhang, Special Member - Keywords:
- Brain blood vessel
two-photon microscopy
hemodynamics
voluntary locomotion
dural vessel
migraine - Abstract:
- Knowledge of the vascular basis of hemodynamic signals and neurovascular coupling is crucial for interpreting brain functional imaging and for developing treatments for neurovascular disorders. To decipher the vascular signals, it is essential to understand the spatial and temporal hemodynamics during natural behaviors. At pia surface, arterioles form an interconnected network that gives rise to penetrating arterioles, which enter into the brain to feed surrounding neurons. Besides the pia mater, the dura mater is another meninge that is densely covered by blood vessels. However, it is not known whether the intracortical arterioles and venules behave similarly as those on the brain surface, whether this hemodynamic response is spatially localized, or whether the dural vessels actively respond as the cortical vessels during natural behavior. To address these questions, we imaged individual vessels in various brain regions using two-photon microscopy, in awake, head-fixed mice during voluntary locomotion. Locomotion drives fast and strong pial arterial dilation, and slow and small venous distension. Their distinct dynamics can be well fitted by a linear convolution model, and can be further applied to separating the fast and slow components in global blood volume signals. To quantify the diameter changes of intracortical vessels more accurately than previous methods, we developed a novel algorithm – Thresholding in Radon Space (TiRS), which makes use of the global structure of the image. We found that surface arterioles and venules dilate significantly more than the intracortical branches. The reduced amplitude of intracortical vessel dilation is attributed to the mechanical restriction by brain tissue. Dural vessels, on the contrary, constrict during locomotion instead of dilating like pial vessels. Under drug-induced migraine condition, dural vessels but not pial vessels are dilated. We conclude that the mechanical properties of the brain may play an important role in sculpting the laminar differences of hemodynamic responses. Under normal physiological condition, dural vessels constrict when pial vessels dilate, and abnormal dilation of dural, but not pial vessels is sufficient to cause headaches.