Most detailed basal ganglia brain cell atlas published

Researchers have published the world's most-detailed atlas of the basal ganglia so far, comprising 25.5 million brain cells from humans, macaques and marmosets. The work is described in a collection of 26 papers published in Cell, Cell Reports, Cell Reports Methods, Cell Systems, Cell Genomics and Neuron.

The atlas and its scope

The basal ganglia are groups of cells deep in the brain that process motor, cognitive, mood and decision-making information. They are linked to neurodegenerative and psychiatric conditions from Parkinson's and Huntington's disease to schizophrenia, bipolar disorder and addiction.

The atlas contains 21 million cells from the brains of six humans, three million cells from three rhesus and cynomolgus macaques, and 1.5 million cells from two marmosets. The researchers also used data from previously published maps of the whole mouse brain.

The collaboration involved hundreds of scientists in nine countries and is part of the BRAIN Initiative Cell Atlas Network (BICAN), a US$500-million project launched in 2022 by the US National Institutes of Health aimed at creating reference maps of mammalian brains.

"It's a massive dictionary that we needed in the field," says Ana Muñoz-Manchado, a neuroscientist at the University of Cádiz in Spain, who studies the basal ganglia in neurodegenerative disorders.

Cross-species findings

By comparing the basal ganglia between primate species, the researchers identified 61 cell types in humans, macaques and marmosets that have been conserved over 76 million years.

The team analysed brain tissue samples from different developmental stages across the lifespan of the species. The work combines information about gene expression, DNA modifications that control gene regulation, recordings of electrical activity, and how DNA is folded inside cell nuclei. Researchers also mapped where each cell is located in the brain and designed a common framework to characterize and annotate the cells.

Michael Hawrylycz, a bioinformatician at the Allen Institute for Brain Science in Seattle, Washington, who took part in the project, said it is "essentially a scaffold on which we can now fairly readily complete the rest of the brain."

Disease-related insights

One study examined 1.1 million cells in the striatum, the basal ganglia's largest structure, from 19 deceased human donors. The researchers identified six zones in the human and macaque striatum that had distinct molecular signatures, each containing distinct populations of neurons and glial cells.

"The cells in these zones all look the same under the microscope, but have very strong transcriptional differences and are strikingly consistent from person to person," said co-author Evan Macosko, a neurobiologist at the Broad Institute of Harvard and MIT in Cambridge, Massachusetts, in a press release from the institute.

Macosko and his colleagues also found that gene expression patterns that distinguished each zone from the other became increasingly similar with age, particularly in brain regions affected by Huntington's or Parkinson's disease.

Another study analysed nearly four million cells in the striatum and prefrontal cortex from 178 deceased adult donors aged from 27 to more than 90. The researchers found that the cellular make-up of the two brain regions varied between people, particularly for non-neuronal cells known as glial cells.

Why it matters

The atlas provides a cross-species reference database that will help researchers understand conditions from Parkinson's disease to addiction. The findings underscore the need for brain cell atlases to account for individual differences in cellular make-up, particularly among glial cells.

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Sources

• nature.com: Massive atlas of brain region linked to a host of diseases is the most detailed yet | Nature

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