Overview
Neuronal activity is intimately linked with changes in metabolism and subsequent changes in cortical blood flow.
Even minor interruptions in flow can adversely effect cognitive function.
Experiments
We consider the nature of blood flow at the level of individual vessels,
from surface arterioles down to single capillaries, in sensory
cortex of rat. The figure shows two-photon excited fluorescence
laser scanning microscopy images of labeled capillaries (left
panel) and red blood cell flow (dark objects; right panel) in
a capillary sequentially scanned at 60 images/s.
Our past work demonstrated that normal blood flow is highly variable
at the level of capillary flow, and that the level of stimulus-induced
changes in flow is comparable to the underlying levels of biological
variability in flow. This variability is believed to originate
in part from recurrent loops in cortical angioarchitecture. Two
avenues of research explore the functional role of these loops.
First, we are reconstructing the entirety of neocortical vasculature
and surrounding neuronal and nonneuronal somata in a block of
approximately ten cortical columns. This should yield a complete
map, at least in a statistical sense, of the connectivity between
surface vessels and deep arteriole-capillary-venule networks.
This work makes use of nonlinear imaging and our all-optical histology
technique.
Second, we are exploring the connection between vascular topology
and the resilience of neocortical vascular networks to local occlusions
to targeted microvessels. We find that flow in the surface network
of leptomeningeal anastomoses is insensitive to single occlusions,
while flow through the subsurface microvascular network is significantly
decremented by a single occlusion. Critically, occlusions to the
penetrating arterioles that connect the surface arterioles with
the subsurface microvasculature result is a columnar-sized region
of ischemia. These results bear on the issue of cortical microstrokes
and transient ischemic occlusion. This work makes use of nonlinear
optical techniques to image as well as perturb blood flow.
Future studies will address flow in the arteriole network relative
to the detailed cortical vasculature, the spatial arrangement
between changes in blood flow and electrical signaling by neocortical
interneurons, and the spatial distribution of oxygen tension throughout
cortex.
Continuing aspects of these studies are performed in collaboration
with Prof. Patrick Lyden and Dr. Beth Friedman at the UCSD School
of Medicine.
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