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Spectrum: Autism Research News

Community Newsletter: Two new mouse brain atlases, plus female mouse behavior

by  /  12 March 2023
Many mouths making conversation, with speech bubbles in red and blue.
Illustration by Laurène Boglio

A melange of mouse research had scientists tweeting up a storm this week.

It all started with “two huge spatial atlases of the whole mouse brain,” tweeted Lukas Valihrach of the Czech Academy of Sciences.

One atlas, developed by researchers at the Allen Institute in Seattle, Washington, combines two single-cell datasets: an RNA sequencing dataset of about 7 million cells, along with a spatial transcriptomic dataset of about 4.3 million cells profiled by way of multiplexed error-robust fluorescence in situ hybridization (MERFISH), a technique Spectrum covered in November 2018.

The atlas “is a foundational resource for deep and integrative investigations of cellular and circuit function, development, and evolution of the mammalian brain,” tweeted Hongkui Zeng of the Allen Institute for Brain Science, in a thread describing her team’s research.

“A new Allen brain atlas for mouse. This is huge, in all aspects,” tweeted Li Wang of the University of California, San Francisco.

Carlos Alvarez of Ohio State University Medical Center asked if Zeng’s team had found “evidence of sex-specific neurons.”

Zeng replied that the team had found a small set that are sex specific or sex dominant in the hypothalamus, amygdala and pallidum areas.

“The spatial combined with the single cell is just [star-struck emoji] – looking forward to using this data!” tweeted Julie Siegenthaler of the University of Colorado.

Delissa McMillen of the Allen Institute replied that “soon all the data we generated in this study will be released for all to use. I can’t wait to see what scientist around the world pull from it.”

Anirban Maitra of the University of Texas MD Anderson Cancer Center shared this image from the paper and quipped, “Jackson Pollock or spatial profiling?”

The second mouse atlas comes from researchers at the Broad Institute in Cambridge, Massachusetts, who used “Slide-seq, a recently developed spatial transcriptomics method with near-cellular resolution,” according to the preprint published 8 March. Spectrum covered Slide-seq in May 2019.

The data underlying the atlas are available online at BrainCellData.org.

“We find minimal marker sets for all cell types, explore activity-regulated genes, and perform analyses of heritability enrichment,” tweeted lead investigator Evan Macosko, a member of the Broad Institute.

“Another incredible whole-brain dataset — what a week!” tweeted Joel Geerling of the University of Iowa.

In another mouse study, published this week in Current Biology, researchers questioned the assumption that female mice complicate experiments because the “estrous cycle makes all female mouse behavior more variable” than males,’ tweeted Sandeep Robert Datta of Harvard University, in a thread describing his team’s research.

The team examined the open-field behavior of female mice at different phases of the estrous cycle, using an approach Datta’s lab pioneered called motion sequencing (MoSeq). The hormonal cycle only negligibly affected female mouse behavior, which is actually less variable than that of males, the team found. Both sexes should be used in experiments, the researchers concluded — and “if you were forced to pick a single sex to use when studying spontaneous exploration, our data suggest that sex should be female,” Datta tweeted.

“Just another nail in the ‘female data are too messy’ coffin!” tweeted Rebecca Shansky of Northeastern University College of Science, who was involved in the study.

“This is super important because even in studies of diseases that predominantly affect women, male mice are used with the assumption that they are more ‘reproducible,’” tweeted Saba Valadkhan of Case Western Reserve University.

Liisa Galea of the University of British Columbia pointed out that “the implication that hormones don’t matter is not correct,” as they do matter, just not more in one sex than the other.

“No more excuses for excluding female mice from studies,” tweeted Silvia Maioli of Karolinska Institutet.

That’s it for this week’s Community Newsletter! If you have any suggestions for interesting social posts you saw in the autism research sphere, feel free to send an email to [email protected].

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Cite this article: https://doi.org/10.53053/WKSV2572