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 wrote 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 what 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 exist. 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. There were two kinds of microglia, which are immune cells that have a specific job in the brain and are only found in humans and chimpanzees, respectively.
Researchers found that the type of microglia that is unique to humans stays the same from childhood to adulthood. This suggests that these cells are more involved in keeping the brain healthy than in 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, so this discovery sparked a lot of attention. More research has shown that FOXP2 is linked to neuropsychiatric disorders like autism, schizophrenia, and epilepsy.
Sestan and colleagues discovered that this gene is expressed specifically in the microglia of 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 we still 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 study was paid for by the National Institutes of Health and the National Institutes of Mental Health.
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.
