Researcher develops method for mapping brain cell change, development in
mice

Date:
July 13, 2020
Source:
Penn State
Summary:
Researchers have developed a new method for studying key moments in
brain development. Researchers are studying how oxytocin receptor
expression changes in normally developing mice and mouse models
of autism spectrum disorder.



FULL STORY ==========================================================================
Penn State researchers have developed a new method for studying key
moments in brain development. Yongsoo Kim, assistant professor of neural
and behavioral sciences at Penn State College of Medicine, is using the
method to understand how oxytocin receptor expression changes in normally developing mice and mouse models of autism spectrum disorder.


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The technique allows scientists to create maps of developing mouse
brains that can display how much of certain cell types are present in
different regions - - and it is a critical first step in being able to
study neurodevelopmental disorders in the brain.

"Key neural connections form during early development," said Kim. "We can
apply this mapping method to study changes of different brain cell types
in developing mouse brains to understand neurodevelopmental disorders
at a cellular level." Kim and his colleagues created maps to help them understand how oxytocin, a neurotransmitter produced by the brain, is
utilized by the brain during the course of early development. Previous
research revealed that oxytocin plays a role in regulating social
behavior, but there is little information on how the receptors that
mediate oxytocin's effect across the brain's neural networks are present
in different parts of the brain across time during development.

The research team hypothesized that different brain regions would have different expression levels of oxytocin receptor (OTR) as individual
brain areas mature. Previous studies investigating oxytocin receptor
expression used methods where only select regions of the brain could be analyzed in portions.

Kim's new technique is able to image whole mouse brains at a cellular resolution using serial two-photon tomography and machine learning-based algorithms to detect fluorescently-labeled neurons that express oxytocin receptors.

The team created template brains from different early postnatal
development periods -- 7, 14, 21 and 28 days after birth. The templates
were created by generating averages of brain images and labelling
key anatomy. They served as a reference point for imaging, detecting
and quantifying the oxytocin receptors during different phases of
development. The results of the study were recently published in Nature Communications.

Kim and colleagues found that OTR expression reached its peak in mouse
brains 21 days after birth, which is equivalent to early childhood
in humans. OTR expression in the hypothalamus continued to increase
until adulthood, indicating that oxytocin signaling may play a role in generating sex-specific behavior. They also studied mice who were unable
to produce oxytocin receptors and noted that there was significantly
reduced synaptic density -- indicating that oxytocin plays a key role
in wiring the brain.

Kim says the same method used to study OTR in this study could be
applied to other brain cell types in order to understand their spatial arrangement across time. The research team built a web-based platform
to host and display the new images for other researchers to access.

"These images will serve as an essential baseline to compare OTR
expression in various mouse models of brain disorders," Kim said. "We
were able to study OTR expression in a mouse model of autism and will
build on these findings by further studying functional and anatomical
changes of different brain cell types and how genetic and environmental
factors may affect brain development in early childhood." Members of
the research team include: Kyra Newmaster, Zachary Nolan, Uree Chon,
Daniel Vanselow and Abigael Weit from the College of Medicine; Manal
Tabbaa and Elizabeth Hammock from Florida State University; and Shizu
Hidema and Katsuhiko Nishimori of the Fukushima Medical University and
Tohoku University Graduate School of Agricultural Science.

This project was supported by funds from the National Institutes of
Health, Tobacco CURE Funds from the Pennsylvania Department of Health, the Japan Agency for Medical Research and Development, and JSPS Grant-in-Aid
for Scientific Research. The content is solely the responsibility of
the authors and does not necessarily represent the official views of
the NIH or other funding agencies.


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


========================================================================== Journal Reference:
1. Kyra T. Newmaster, Zachary T. Nolan, Uree Chon, Daniel J. Vanselow,
Abigael R. Weit, Manal Tabbaa, Shizu Hidema, Katsuhiko
Nishimori, Elizabeth A. D. Hammock, Yongsoo Kim. Quantitative
cellular-resolution map of the oxytocin receptor in postnatally
developing mouse brains.

Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-15659-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200713125514.htm

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