More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction
Abstract
Our understanding of how capillary blood flow and oxygen distribute across cortical layers to meet the local metabolic demand is incomplete. We addressed this question by using two-photon imaging of resting-state microvascular oxygen partial pressure (PO2) and flow in the whisker barrel cortex in awake mice. Our measurements in layers I-V show that the capillary red-blood-cell flux and oxygenation heterogeneity, and the intracapillary resistance to oxygen delivery, all decrease with depth, reaching a minimum around layer IV, while the depth-dependent oxygen extraction fraction is increased in layer IV, where oxygen demand is presumably the highest. Our findings suggest that more homogeneous distribution of the physiological observables relevant to oxygen transport to tissue is an important part of the microvascular network adaptation to local brain metabolism. These results will inform the biophysical models of layer-specific cerebral oxygen delivery and consumption and improve our understanding of the diseases that affect cerebral microcirculation.
Data availability
All data generated or analyzed during this study are included in this paper and the supporting files.
Article and author information
Author details
Funding
National Institutes of Health (NS091230)
- Sava Sakadžić
National Institutes of Health (MH111359)
- Sava Sakadžić
National Institutes of Health (EB018464)
- Sava Sakadžić
National Institutes of Health (NS092986)
- Sava Sakadžić
National Institutes of Health (NS055104)
- Sava Sakadžić
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal surgical and experimental procedures were conducted following the Guide for the Care and Use of Laboratory Animals and approved by the Massachusetts General Hospital Subcommittee on Research Animal Care (Protocol No.: 2007N000050).
Reviewing Editor
- Serge Charpak, Institut National de la Santé et de la Recherche Médicale, Université Paris Descartes, France
Version history
- Received: September 24, 2018
- Accepted: July 1, 2019
- Accepted Manuscript published: July 15, 2019 (version 1)
- Version of Record published: July 17, 2019 (version 2)
Copyright
© 2019, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,302
- Page views
-
- 322
- Downloads
-
- 54
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
How does the human brain combine information across the eyes? It has been known for many years that cortical normalization mechanisms implement ‘ocularity invariance’: equalizing neural responses to spatial patterns presented either monocularly or binocularly. Here, we used a novel combination of electrophysiology, psychophysics, pupillometry, and computational modeling to ask whether this invariance also holds for flickering luminance stimuli with no spatial contrast. We find dramatic violations of ocularity invariance for these stimuli, both in the cortex and also in the subcortical pathways that govern pupil diameter. Specifically, we find substantial binocular facilitation in both pathways with the effect being strongest in the cortex. Near-linear binocular additivity (instead of ocularity invariance) was also found using a perceptual luminance matching task. Ocularity invariance is, therefore, not a ubiquitous feature of visual processing, and the brain appears to repurpose a generic normalization algorithm for different visual functions by adjusting the amount of interocular suppression.
-
- Neuroscience
Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in Drosophila melanogaster indicates that taste responses also exhibit plasticity through experience-dependent changes in mushroom body circuits. In this study, we develop a novel taste learning paradigm using closed-loop optogenetics. We find that appetitive and aversive taste memories can be formed by pairing gustatory stimuli with optogenetic activation of sensory neurons or dopaminergic neurons encoding reward or punishment. As with olfactory memories, distinct dopaminergic subpopulations drive the parallel formation of short- and long-term appetitive memories. Long-term memories are protein synthesis-dependent and have energetic requirements that are satisfied by a variety of caloric food sources or by direct stimulation of MB-MP1 dopaminergic neurons. Our paradigm affords new opportunities to probe plasticity mechanisms within the taste system and understand the extent to which taste responses depend on experience.