Live imaging method brings structural information to mapping of brain
function

Date:
September 17, 2020
Source:
Picower Institute at MIT
Summary:
Neuroscientists distinguish brain regions based on what they do,
but now have a new way to overlay information about how they are
built, too.



FULL STORY ==========================================================================
To understand the massive capabilities and complexities of the brain, neuroscientists segment it into regions based on what they appear
to do -- like processing what we sense or how to move. What's been
lacking, however, is an ability to tie those functional maps precisely
and consistently to matching distinctions of physical structure,
especially in live animals while they are performing the functions of
interest. In a new study, MIT researchers demonstrate a new way to do
that, providing an unprecedented pairing of functional mapping in live
mice with distinguishing structural information for each region all the
way through the cortex into deeper tissue below.


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"Our study shows for the first time that structural and functional
coupling of visual areas in the mouse brain can be detected at
sub-cellular resolution in vivo," wrote the authors based in the lab of Mriganka Sur, Newton Professor of Neuroscience in The Picower Institute
for Learning and Memory and the Department of Brain and Cognitive Sciences
at MIT.

The technique could give scientists more precise ways to distinguish
the borders and contents of regions they wish to study and could help
them better understand the way that structural distinctions develop
within individuals in different functional regions over time. Sur's lab,
for instance, is intensely interested in understanding the especially
complex development of vision.

Humans have 35 or so distinct functional regions that contribute to
processing vision, Sur notes, and even mice have 10.

"There is something profound in the way that vision is represented and
created in mammalian brains," Sur said. "Where do these areas come from,
what do they mean and what do they do? It has not been easy to understand
how they differ.

The critical thing is to precisely map or match the functional
representation of each area with its anatomical uniqueness." Combining function and structure To develop tools to help answer those questions,
postdoc Murat Yildirim led the study published in Biomedical Optics
Express. In it he describes how the research team combined a method of
charting functional areas -- retinotopic mapping -- with deep structural information measured by a technology he has helped to pioneer --
third-harmonic generation (THG) three-photon microscopy.



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In retinotopic mapping, researchers can identify functional regions by engineering neurons to flash when they become electrically active (and
show changes in calcium) in response to a particular stimulation. For
example, scientists could show a mouse a pattern moving across a screen
and mark where neurons light up, with each area showing a characteristic location and pattern of response.

Three-photon microscopy can finely resolve individual cells and their
smaller substructures as deep as a millimeter or more -- enough to see
all the way through the cortex. THG, meanwhile, adds the capability to
finely resolve both blood vessels and the fibers of a material called
myelin that wrap the long, tendrilous axons of many neurons. THG does
not require adding any labeling dyes or chemicals.

Crucially, THG yields an important optical measure called effective
attenuation length (EAL), which is a measure of how much the light is
absorbed or scattered as it moves through the tissue. In the study,
Yildirim and co-authors show that EAL specifically depends on each
region's unique architecture of cells, blood vessels and myelin. They
measured EAL in each of six visual functional regions and showed that the
EAL significantly differed among neighboring visual areas, providing a structural signature of sorts for each functional area. Their measurements
were so precise, in fact, that they could show how EAL varied within
functional regions, being most unique toward the middle and blending
closer to the values of neighboring regions out toward the borders.

In other words, by combining the retinotopic mapping with THG three-photon microscopy, Yildirim said, scientists can identify distinct regions by
both their function and structure while continuing to work with animals in
live experiments. This can produce more accurate and faster results than
making observations during behavior and then dissecting tissue in hopes of relocating those same exact positions in preserved brain sections later.

"We would like to combine the strength of retinotopic mapping with
three-photon imaging to get more structural information," Yildirim
said. "Otherwise there may be some discrepancies when you do the live
imaging of brain activity but then take the tissue out, stain it and
try to find the same region." Especially as three-photon microscopy
gains wider adoption and imaging speeds improve -- right now imaging
a millimeter deep column of cortex takes about 15 minutes, the authors acknowledge -- the team expects its new method could be used not only
for studies of the visual system but also in regions all around the
cortex. Moreover it may help characterize disease states as well as
healthy brain structure and function.

"This advance should enable similar studies of structural and functional coupling in other sensory and non-sensory cortical areas in the brains of
mice and other animal models," they wrote. "We believe that the structural
and functional correlation in visual areas that we describe for the first
time points to crucial developmental mechanisms that set up these areas,
thus our work would lead to a better fundamental understanding of brain development, and of disorders such as Alzheimer's, stroke and aging."
The National Institutes of Health, the National Science Foundation, The
JPB Foundation and the Massachusetts Life Sciences Initiative provided
funding for the study.


========================================================================== Story Source: Materials provided by Picower_Institute_at_MIT. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Murat Yildirim, Ming Hu, Nhat M. Le, Hiroki Sugihara, Peter
T. C. So,
Mriganka Sur. Quantitative third-harmonic generation imaging of
mouse visual cortex areas reveals correlations between functional
maps and structural substrates. Biomedical Optics Express, 2020;
11 (10): 5650 DOI: 10.1364/BOE.396962 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200917084111.htm

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