Drew PJ, Shih AY, Kleinfeld DFluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. Proc Natl Acad Sci USA 108:8473-8478

Departments of Physics and Neurobiology and Center for Neural Circuits and Behavior, University of California, San Diego, CA 92093, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2011; 108(20):8473-8. DOI: 10.1073/pnas.1100428108
Source: PubMed


Neural activity in the brain is followed by localized changes in blood flow and volume. We address the relative change in volume for arteriole vs. venous blood within primary vibrissa cortex of awake, head-fixed mice. Two-photon laser-scanning microscopy was used to measure spontaneous and sensory evoked changes in flow and volume at the level of single vessels. We find that arterioles exhibit slow (<1 Hz) spontaneous increases in their diameter, as well as pronounced dilation in response to both punctate and prolonged stimulation of the contralateral vibrissae. In contrast, venules dilate only in response to prolonged stimulation. We conclude that stimulation that occurs on the time scale of natural stimuli leads to a net increase in the reservoir of arteriole blood. Thus, a "bagpipe" model that highlights arteriole dilation should augment the current "balloon" model of venous distension in the interpretation of fMRI images.

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Available from: Andy Shih, May 11, 2015
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    • "We anticipate that under anesthetics that have minimal effect on vascular tone, a similar restriction of intracortical vessel dilation should take place as in awake animals, as brain tissue elasticity measurements made under isoflurane (Pattison et al., 2010) are similar to those in awake humans (Mousavi et al., 2014). We think that the restriction of intracortical vessel dilation that we see here will not just occur during locomotion, but also generalize in response to other stimuli, since the dynamics and amplitude of surface vessel dilation in response to voluntary locomotion (Huo et al., 2015) are nearly identical to those evoked by stimulation of the vibrissae (Drew et al., 2011). It should be kept in mind that dilation of blood vessels will displace CSF. "
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    ABSTRACT: Understanding the spatial dynamics of dilation in the cerebral vasculature is essential for deciphering the vascular basis of hemodynamic signals in the brain. We used two-photon microscopy to image neural activity and vascular dynamics in the somatosensory cortex of awake behaving mice during voluntary locomotion. Arterial dilations within the histologically-defined forelimb/hindlimb (FL/HL) representation were larger than arterial dilations in the somatosensory cortex immediately outside the FL/HL representation, demonstrating that the vascular response during natural behaviors was spatially localized. Surprisingly, we found that locomotion drove dilations in surface vessels that were nearly three times the amplitude of intracortical vessel dilations. The smaller dilations of the intracortical arterioles were not due to saturation of dilation. Anatomical imaging revealed that, unlike surface vessels, intracortical vessels were tightly enclosed by brain tissue. A mathematical model showed that mechanical restriction by the brain tissue surrounding intracortical vessels could account for the reduced amplitude of intracortical vessel dilation relative to surface vessels. Thus, under normal conditions, the mechanical properties of the brain may play an important role in sculpting the laminar differences of hemodynamic responses. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 05/2015; 115. DOI:10.1016/j.neuroimage.2015.04.054 · 6.36 Impact Factor
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    • "The diameters of veins took tens of seconds to return to baseline (Fig. 2C). Locomotion-driven arterial and venous dilations were very similar in magnitude and time course to those evoked by vibrissae stimulation in stationary mice, and exhibited the same spontaneous dilations in the absence of overt sensory stimulation (Drew et al., 2011) (see Supplementary Fig. S1). However these dilations are substantially larger than those of vessels in anesthetized animals (Drew et al., 2010; Tian et al., 2011), consistent with the observation that anesthesia profoundly disrupts the activity of neurons (Chapin and Lin, 1984) and astrocytes (Thrane et al., 2012), making anesthesia more akin to a coma than reflecting normal brain function (Brown et al., 2010). "
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    ABSTRACT: Voluntary locomotion is accompanied by large increases in cortical activity and localized increases in cerebral blood volume (CBV). We sought to quantitatively determine the spatial and temporal dynamics of voluntary locomotion-evoked cerebral hemodynamic changes. We measured single vessel dilations using two-photon microscopy and cortex-wide changes in CBV-related signal using intrinsic optical signal (IOS) imaging in head-fixed mice freely locomoting on a spherical treadmill. During bouts of locomotion, arteries dilated rapidly, while veins distended slightly and recovered slowly. The dynamics of diameter changes of both vessel types could be captured using a simple linear convolution model. Using these single vessel measurements, we developed a novel analysis approach to separate out spatially and temporally distinct arterial and venous components of the location-specific hemodynamic response functions (HRF) for IOS. The HRF of each pixel of was well fit by a sum of a fast arterial and a slow venous component. The HRFs of pixels in the limb representations of somatosensory cortex had a large arterial contribution, while in the frontal cortex the arterial contribution to the HRF was negligible. The venous contribution was much less localized, and was substantial in the frontal cortex. The spatial pattern and amplitude of these HRFs in response to locomotion in the cortex were robust across imaging sessions. Separating the more localized, the arterial component from the diffuse venous signals will be useful for dealing with the dynamic signals generated by naturalistic stimuli. Copyright © 2014. Published by Elsevier Inc.
    NeuroImage 10/2014; 105. DOI:10.1016/j.neuroimage.2014.10.030 · 6.36 Impact Factor
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    • "As with other ubiquitous scattering-based techniques such as laser Doppler, the effects of RBC orientation on scattering in OCT remains an issue that warrants future investigation. Provided that RBC orientation confounds could be mitigated, OCT may prove to be a valuable tool to study RBC changes in pial veins during long stimuli (Drew et al., 2011). "
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    ABSTRACT: The BOLD (blood-oxygen-level dependent) fMRI (functional Magnetic Resonance Imaging) signal is shaped, in part, by changes in red blood cell (RBC) content and flow across vascular compartments over time. These complex dynamics have been challenging to characterize directly due to a lack of appropriate imaging modalities. In this study, making use of infrared light scattering from RBCs, depth-resolved Optical Coherence Tomography (OCT) angiography was applied to image laminar functional hyperemia in the rat somatosensory cortex. After defining and validating depth-specific metrics for changes in RBC content and speed, laminar hemodynamic responses in microvasculature up to cortical depths of >1 mm were measured during a forepaw stimulus. The results provide a comprehensive picture of when and where changes in RBC content and speed occur during and immediately following cortical activation. In summary, the earliest and largest microvascular RBC content changes occurred in the middle cortical layers, while post-stimulus undershoots were most prominent superficially. These laminar variations in positive and negative responses paralleled known distributions of excitatory and inhibitory synapses, suggesting neuronal underpinnings. Additionally, the RBC speed response consistently returned to baseline more promptly than RBC content after the stimulus across cortical layers, supporting a "flow-volume mismatch" of hemodynamic origin.
    NeuroImage 08/2014; 102. DOI:10.1016/j.neuroimage.2014.08.004 · 6.36 Impact Factor
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