Drop-seq reveals new neuron type found only in primate brains

Study finds key differences between human and lab animal brains, which could help scientists improve studies on neuropsychiatric disease.

Kirsten Levandowski and Heather Zaniewski

Neuropsychiatric illnesses like schizophrenia and autism are a complex interplay of brain chemicals, environment, and genetics that requires careful study to understand the root causes. Scientists have traditionally relied on samples taken from mice and non-human primates to study how these diseases develop. But the question has lingered: are the brains of these subjects similar enough to humans to yield useful insights?

Now work from the Broad Institute of MIT and Harvard is pointing towards an answer. In a study published in Nature, researchers from the Broad’s Stanley Center for Psychiatric Research report several key differences in the brains of ferrets, mice, nonhuman primates, and humans, all focused on a type of neuron called interneurons. Most surprisingly, the team found a new type of interneuron only in primates, located in a part of the brain called the striatum, which is associated with Huntington’s disease and potentially schizophrenia.

One of the tools the researchers used was Drop-seq, a high-throughput single nucleus RNA sequencing technique developed by McCarroll’s lab, to classify the roles and locations of more than 184,000 telencephalic interneurons in the brains of ferrets, humans, macaques, marmosets, and mice. Using tissue from frozen samples, the team isolated the nuclei of interneurons from the cortex, the hippocampus, and the striatum, and profiled the RNA from the cells.

The researchers thought that because interneurons are found in all vertebrates, the cells would be relatively static from species to species.

“But with these sensitive measurements and a lot of data from the various species, we got a different picture about how lively interneurons are, in terms of the ways that evolution has tweaked their programs or their populations from one species to the next,” said Krienen.

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Source – The Broad Institute

Krienen FM, Goldman M, Zhang Q et al. (2020) Innovations present in the primate interneuron repertoire. Nature [online ahead of print. [abstract].

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