Inside your brain

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The chimpanzee is one of our closest animal relatives, but when it comes to how our brains work—and sometimes, don’t work—humans set themselves apart. In a recent study, Yale neuroscientists took a cell-by-cell look at human and nonhuman primate brains to better understand where we diverge from our primate brethren.
“This is the only reason why I’m a scientist: trying to understand what makes us human,” says Nenad Sestan ’99PhD, professor of neuroscience.

The researchers focused on the dorsolateral prefrontal cortex, a versatile part of the brain that controls cognitive tasks such as planning and memory—critical functions that may lead to disease if disrupted.

When technology for isolating individual cell nuclei from delicate brain samples finally emerged, Sestan jumped at the opportunity to do a study he had long dreamt of. His team carefully extracted 600,000 nuclei from cells in the brains of humans, chimpanzees, macaques, and marmosets. “We generated a large treasure chest of data,” says Mario Skarica, a neurobiologist and co–first author of this study.

They could now measure thousands of RNA molecules that each told a story about a particular cell’s skills: some cells could send messages to other parts of the brain; other cells could produce important brain chemicals.

Sestan’s team was especially intrigued by the differences between the same types of cells in humans and nonhuman primates. In some cases, humans seemed to produce more RNA linked to certain chemicals such as retinoic acid and dopamine, which are involved in brain function and development.

The researchers also found that some molecules linked to neuropsychiatric disease appeared in unexpected cells in humans, and not in nonhuman primates. This could help researchers study notoriously difficult-to-treat brain diseases. Dopamine, for example, is a target for treatments in many diseases, but scientists did not previously know whether dopamine-making cells existed in the human prefrontal cortex.

Sestan admits he hasn’t yet figured out what makes us human. But with this study, he says, “We got one step closer.”