What makes the human brain different? Study reveals clues



What distinguishes the human brain from all other animal brains, even those of our closest primate relatives? Yale researchers examined the different cell types in the prefrontal cortex of four different species of primates, and they found traits that were species-specific, notably human-specific, they write in the journal Science on August 25.

Additionally, they discovered that part of what makes us human may also predispose us to neuropsychiatric illnesses.

The dorsolateral prefrontal cortex (dlPFC), a part of the brain that is particular to primates and necessary for higher-order cognition, was the focus of the study. They assessed the gene expression levels in millions of cells taken from the dlPFC of adult humans, chimpanzees, macaques, and marmoset primates using a single cell RNA-sequencing approach.

Nenad Sestan, the Harvey and Kate Cushing Professor of Neuroscience at Yale, professor of comparative medicine, genetics, and psychiatry, and the lead senior author of the paper, said: "Today, we view the dorsolateral prefrontal cortex as the core component of human identity, but still, we don't know what makes this unique in humans and distinguishes us from other primate species." "We now have additional hints,"

In order to respond to this, the researchers first questioned whether any cell types that are only found in humans or the other non-human primate species under study. They discovered 109 shared primate cell types after grouping cells with comparable expression profiles, but they also found five that weren't shared by all species. These included two distinct types of microglia, or immune cells with a specific function in the brain, found only in humans and chimpanzees, respectively.

Researchers discovered that the human-specific microglia type persists throughout development and adulthood, indicating that these cells are more involved in maintaining healthy brain function than fighting disease.

Glia cells, particularly microglia, are extremely sensitive to these variations since we humans lead a very different lifestyle from other primate species, according to Sestan. The type of microglia seen in the human brain may be an indication of an immunological reaction to the surroundings.

Another human-specific surprise was found when the gene FOXP2 was examined for expression in the microglia. Variants of FOXP2 have been related to verbal dyspraxia, a disorder in which sufferers struggle to produce language or speech, thus this discovery sparked a lot of attention. Additional research has revealed a connection between FOXP2 and other neuropsychiatric disorders, including autism, schizophrenia, and epilepsy.

Sestan and colleagues discovered that this gene expresses specifically in microglia from humans and a subset of excitatory neurons from primates.

According to Shaojie Ma, a postdoctoral associate in Sestan's group and co-lead author, "FOXP2 has captivated many scientists for decades, but still we had no concept of what makes it distinctive in humans versus other primate species." The FOXP2 findings open up new avenues for the study of language and diseases, which makes us very excited.

The National Institutes of Health and National Institute of Mental Health provided funding for the study.

Co-senior authors Andre Sousa, an assistant professor of neuroscience at the University of Wisconsin-Madison, co-lead author Mario Skarica, an associate research scientist in neuroscience at Yale School of Medicine, and co-senior author Stephen M. Strittmatter, the Vincent Coates Professor of Neurology and Professor of Neuroscience at Yale, chair of the Department of Neuroscience, and director of the Kavli Institute for Neuroscience, are also contributors.

Yale University

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